CD163
Scavenger receptor cysteine-rich type 1 protein M130 precursor (Hemoglobin scavenger receptor) (CD163 antigen) [Contains: Soluble CD163 (sCD163)] [M130]
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Does sodium tanshinone IIA sulfonate (STS) induce cellular senescence in endometriotic lesions and thus restrict lesional development and fibrogenesis in a recently established mouse model of deep endometriosis? Prospective randomized animal experiment in which deep endometriosis was induced in female Balb/C mice, which were then randomly divided into three groups (low-dose STS, high-dose STS and inert vehicle control) and received treatment for 2 weeks. All mice were then sacrificed and their lesions excised and harvested. Lesion weight was quantified and all lesion samples were subjected to histochemical analysis of the extent of lesional fibrosis by Masson trichrome staining, and of cellular senescence by senescence-associated β-galactosidase (SA-β-gal), along with immunohistochemistry analyses of p53, CCN1, activate Salvador 1 (Sav1), hyaluronan synthase 2 (HAS2), survivin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and CD163-positive M2 macrophages. Plasma P-selectin and hyaluronic acid levels were also quantified. Hotplate testing was also administered before the induction, then before and after treatment. STS treatment resulted in significantly reduced lesion weight, stalled lesional fibrogenesis and improved hyperalgesia, seemingly through the induction of cellular senescence by activating p53, Sav1 and CCN1 while suppressing HAS2, survivin and GM-CSF, resulting in increased apoptosis and reduced lesional infiltration of alternatively activated macrophages. In addition, STS treatment significantly reduced the plasma concentration of P-selectin and hyaluronic acid, possibly leading to reduced lesional platelet aggregation. STS appears to be a promising compound for treating endometriosis. The results suggest that senescence may restrict lesional progression and fibrogenesis, and targeting the senescence pathway may have desirable therapeutic potential.
Keywords
- Deep endometriosis
- Fibrogenesis
- Mouse
- Senescence
- Sodium tanshinone IIA sulfonate
Macrophages have vital roles in innate immunity by modulating the inflammatory response via their ability to alter their phenotype from pro-inflammatory (M1) to anti-inflammatory (M2). Aging increases activation of the innate immune system, and macrophage numbers increase in the aged liver. Since macrophages also produce free radical molecules, they are a potential source of age-related oxidative injury in the liver. This study evaluated macrophage phenotype in the aged liver and whether the increase in the number of macrophages with aging is associated with enhanced hepatic oxidative stress. Hepatic macrophage phenotype and oxidative stress were evaluated 2 days after a single intraperitoneal injection of saline or gadolinium chloride (GdCl , 10 mg/kg) in young (6 months) and aged (24 months) Fischer 344 rats. GdCl has been shown to decrease the expression of macrophage-specific markers and impair macrophage phagocytosis in the liver. Saline-treated aged rats demonstrated greater numbers of both M1 (HO-1 /iNOS ) and M2 (HO-1 /CD163 ) macrophages, without evidence of a phenotypic shift. GdCl did not alter levels of dihydroethidium fluorescence or malondialdehyde, suggesting that macrophages are not a major contributor to steady-state levels of oxidative stress. However, GdCl decreased M1 and M2 macrophage markers in both age groups, an effect that was attenuated in aged rats. In old animals, GdCl decreased iNOS expression to a greater extent than HO-1 or CD163. These results suggest a novel effect of aging on macrophage biology and that GdCl shifts hepatic macrophage polarization to the M2 phenotype in aged animals.
MeSH Terms
- Aging
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
- Gadolinium
- Liver
- Macrophages
- Male
- Phenotype
- Rats
Keywords
- Fluorescence microscopy
- Immunolabelling
- Inflammation
- Kupffer cells
- Oxidative stress
- iNOS
M2 macrophages are often detected in oral squamous cell carcinoma (OSCC), which, influenced by hypoxic conditions, appear to have high angiogenesis-inducing capacity. However, the effects of immunosenescence on tumor-associated macrophages (TAMs) and angiogenesis in OSCC are unknown. Fifty-seven OSCCs were divided into 3 groups (I: <40 years [n = 17]; II: 40-65 years [n = 20]; III: >65 years [n = 20]). Immunohistochemistry for CD68 and CD163 (TAMs), and CD34 and D2-40 for microvessel density (MVD), microvessel area (MVA), and total vascular area (TVA) were performed. All groups showed similar clinicopathological and immunohistochemical findings. Similar CD68 and CD163 expression, confirmed a M2 phenotype. MVD, MVA, and TVA were similar, however, with significant predominance of blood vessels. No significant correlation between macrophage and angiogenic markers was observed. A similar TAM and angiogenesis profile suggests the participation of other mechanisms, instead immunosenescence, in young and elderly OSCC patients.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Antigens, CD
- Antigens, Differentiation, Myelomonocytic
- Carcinoma, Squamous Cell
- Female
- Humans
- Immunohistochemistry
- Immunosenescence
- Macrophages
- Male
- Middle Aged
- Mouth Neoplasms
- Neovascularization, Pathologic
- Receptors, Cell Surface
- Tumor Microenvironment
Keywords
- M1 and M2 macrophages
- angiogenesis
- immunohistochemistry
- immunosenescence
- oral squamous cell carcinoma
Background and Purpose- Early erythrolysis in the hematoma contributes to brain injury after intracerebral hemorrhage (ICH). This study investigated the effects of N-acetylheparin, a complement inhibitor, and aurin tricarboxylic acid, a membrane attack complex inhibitor, on early erythrolysis, brain iron deposition, and brain injury in aged rats. Methods- There were 3 parts in the study. First, aged (18 months old) male Fischer 344 rats had an ICH. The time course of erythrolysis in the hematoma was determined by T2* weighted magnetic resonance imaging, and the expression of CD163 was examined. Second, aged rats had an ICH with N-acetylheparin or vehicle. Rats were euthanized at days 1, 3, and 28 after magnetic resonance imaging (T2-, T2*-weighted, and T2* array) and behavioral tests. Brains were used for immunohistochemistry. Third, aged rats had an ICH with avaurin tricarboxylic acid or vehicle. The rats had magnetic resonance imaging and behavioral tests and were euthanized at day 3. Brains were used for immunohistochemistry. Results- Early erythrolysis occurred within the clot in aged F344 rats. There were increased numbers of CD163-positive cells after ICH. Almost all perihematomal CD163-positive cells were microglia/macrophages, while positive neurons were found more distant from the hematoma. Coinjection of N-acetylheparin attenuated erythrolysis, iron accumulation, CD163 expression, microglia activation, brain swelling, and neuronal death in the acute phase, as well as reducing brain atrophy and neurological deficits in the chronic phase. Coinjection of aurin tricarboxylic acid also reduced erythrolysis and ICH-induced brain injury. Conclusions- Inhibiting complement activation resulted in less erythrolysis and brain injury after ICH.
MeSH Terms
- Aging
- Animals
- Antigens, CD
- Antigens, Differentiation, Myelomonocytic
- Aurintricarboxylic Acid
- Brain Edema
- Brain Injuries
- Complement Inactivating Agents
- Erythrocytes
- Hemolysis
- Heparin
- Intracranial Hemorrhages
- Ischemic Attack, Transient
- Macrophage Activation
- Male
- Microglia
- Rats
- Rats, Inbred F344
- Receptors, Cell Surface
Keywords
- CD163
- aurin tricarboxylic acid
- intracerebral hemorrhage
- microglia
- n-acetylheparin
The key to newer therapeutic and eradication approaches often lies in understanding slow disease progression in HIV infection. The paediatric population has been poorly studied in this regard. We aimed to describe a cohort of perinatally infected long-term nonprogressor (LTNP) children living with HIV in India and to evaluate the immune biomarkers of disease progression. LTNPs (ART-naïve, with a CD4 count ≥ 500 cells/μL at age ≥ 7 years) among the cohort of HIV-infected children were identified and monitored longitudinally, and their CD4 T-cell counts and plasma viral loads were measured every 6 months. The plasma monocyte/macrophage activation markers, namely soluble CD14 (sCD14), soluble CD163 (sCD163) and interferon-inducible protein-10 (IP-10) were measured by enzyme-linked immunosorbent assay (ELISA) in LTNPs and progressors. The Mann-Whitney U-test was used to compare the two groups and P values < 0.05 were considered statistically significant. Spearman's rank or Pearson's correlation coefficient (r) was calculated to determine the associations between variables. Among 378 children living with HIV-1 surveyed in our cohort, 40 (10.6%) were LTNPs. Longitudinal analysis of the LTNP data showed that both CD4 count and viral load declined significantly with age (P < 0.0001 for both). Plasma sCD14 levels were significantly (P < 0.005) higher in progressors and sCD163 levels were significantly (P < 0.0001) higher in LTNPs. The prevalence of LTNPs in our cohort of perinatally infected children living with HIV was 10.6%. We observed a trend for associations between the increasing sCD163 monocyte/macrophage activation marker levels, declining CD4 counts and the gradual loss of nonprogressor status with age in the LTNPs. These findings underscore the need for early antiretroviral therapy in those children with proven slow disease progression.
MeSH Terms
- Adolescent
- Aging
- Antigens, CD
- Antigens, Differentiation, Myelomonocytic
- Biomarkers
- CD4 Lymphocyte Count
- Chemokine CXCL10
- Child
- Cross-Sectional Studies
- Disease Progression
- Female
- HIV Infections
- HIV Long-Term Survivors
- HIV-1
- Humans
- India
- Infectious Disease Transmission, Vertical
- Longitudinal Studies
- Male
- Monocytes
- Prevalence
- Receptors, Cell Surface
- Viral Load
Keywords
- HIV-1
- children
- immune biomarkers
- long-term nonprogressors
- monocyte activation
Multiple sclerosis (MS) is a chronic inflammatory CNS disease, which causes demyelinated lesions and damages white and gray matter regions. Aging is a significant factor in the progression of MS, and microglia, the immune cells of the CNS tissue, play an important role in all disease stages. During aging, microglia are functionally altered. These age-related changes probably already begin early and might influence the progression of CNS pathologies. The aim of the present study was to investigate whether microglia in the middle-aged CNS already react differently to demyelination. For this purpose, several microglia markers (ionized calcium binding adaptor molecule 1 (Iba-1), P2RY12, F4/80, CD68, major histocompatibility complex II (MHCII), macrophage receptor with collagenous structure (Marco), Translocator protein 18 kD ([[TSPO]]), CD206, and CD163) were analyzed in the acute cuprizone demyelination model in young (2-month-old) and middle-aged (10-month-old) mice. In addition, microglial proliferation was quantified using double-labeling with proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU), which was injected with the onset of remyelination. To compare age-related microglial changes during de- and remyelination in both gray and white matter, the hilus of the dorsal hippocampal dentate gyrus (DG) and the splenium of the corpus callosum (CC) were analyzed in parallel. Age-related changes in microglia of healthy controls were more pronounced in the analyzed gray matter region (higher levels of F4/80 and Marco as well as lower expression of CD68 in middle-aged mice). During de- and remyelination, a stronger increase of the microglial markers Iba-1, CD68 and [[TSPO]] was observed in the splenium of the younger groups. There was a significant reduction of P2RY12 during demyelination, however, this was age- and region-dependent. The induction of the anti-inflammatory markers CD206 and CD163 was stronger in the middle-aged group, but also differed between the two analyzed regions. De- and remyelination led to a significant increase in PCNA microglia only in young groups within the white matter region. The number of BrdU microglia was not changed during de- or remyelination. These results clearly show that microglia are already altered during middle-age and also react differently to CNS demyelination, however, this is highly region-dependent.
Keywords
- P2RY12
- TSPO
- aging
- corpus callosum
- cuprizone
- demyelination
- hippocampus
- microglia
Macrophage polarization is a candidate biomarker of disease-related inflammatory status, but its modulation during aging has not been investigated. To do this, the M1/M2 profile was assessed by CD80/CD163 gating in classical (CD14 CD16 ), intermediate (CD14 CD16 ), and non-classical (CD14 CD16 ) monocytes from 31 healthy subjects (CTRs) of different ages. Cytofluorimetric analysis showed a significantly different CD80/CD163 distribution in the three subsets, as more than 80% of classical and intermediate monocytes were CD80 CD163 , whereas most non-classical monocytes were CD80 CD163 and CD163 . Non-classical CD163 monocytes were significantly higher whereas classical CD163 and CD80 CD163 monocytes significantly lower in older than younger CTRs (cut-off, 65 years), suggesting different age-related trends for M2 subsets. To establish whether an M1/M2 imbalance could be associated with disease, 21 patients with acute myocardial infarction (AMI) were compared with older CTRs. The AMI patients showed a significantly decreased proportion of CD163 CD80 and an increased proportion of CD163 and CD163 CD80 cells among classical monocytes, opposite trends to those observed in healthy aging. Moreover, a significantly greater proportion of intermediate and non-classical CD80 monocytes suggested a shift to a pro-inflammatory phenotype. Overall, CD163/CD80 cytofluorimetric characterization of circulating monocytes provides additional information about their polarization and could be an innovative tool to monitor aging.
MeSH Terms
- Aged
- Antigens, CD
- Biomarkers
- Female
- Flow Cytometry
- Gene Expression Regulation
- Humans
- Inflammation
- Killer Cells, Natural
- Macrophages
- Male
- Middle Aged
- Monocytes
- Myocardial Infarction
- T-Lymphocytes
Keywords
- M1/M2 monocytes
- NK/NK-T cells
- acute myocardial infarction
- aging
We analyzed the impact of age, sex, and CMV on blood monocyte and dendritic cell (DC) subpopulations in 256 healthy individuals aged from 19 to 96 years. Flow cytometry was performed on whole blood within the 4 h following blood drawing. Myeloid (mDC) and plasmacytoid DC (pDC), classical, intermediate, and nonclassical monocytes were enumerated by means of TruCount tubes (BD Biosciences). We provided reference values for mDC, pDC and the three monocyte subpopulations. The numbers of classical, intermediate, and nonclassical monocytes slightly increased with age while the numbers of mDC and pDC did not vary significantly. The level of expression of CD64 and CD163 on monocytes significantly increased with age while HLA-DR expression did not vary significantly. More precisely, CD163 expression level on intermediate monocyte slightly increased with age in women only (Spearman P = 0.019) while CD64 expression increased on monocytes in CMV-positive individuals only. We observed that sex had almost no impact on the numbers of monocytes and DC and on their expression level of CD64 and HLA-DR. We observed a significant decrease in the numbers of pDC with age in CMV-positive individuals, but not in CMV negative individuals. This suggests that the lifelong subclinical infection by CMV could influence the number of circulating DC of lymphoid origin. In contrast, CMV serostatus had no significant impact on absolute numbers of mDC and monocytes.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Antibodies, Viral
- Blood Cells
- Cell Count
- Cell Separation
- Cytomegalovirus
- Cytomegalovirus Infections
- Dendritic Cells
- Female
- Flow Cytometry
- Humans
- Immunophenotyping
- Male
- Middle Aged
- Monocytes
- Sex
- Young Adult
The pro- and anti-inflammatory macrophages are associated with insulin sensitivity and skeletal muscle regeneration. Infiltrating macrophages in skeletal muscle during a period of physical inactivity and subsequent reloading/rehabilitation in older adults is unknown, but may provide insight into mechanisms related to the development of metabolic disease and changes in muscle cell size. The purpose of this study was to determine if skeletal muscle macrophage infiltration is modulated differently between young and older adults after bed rest and exercise rehabilitation and if these responses are related to muscle and insulin sensitivity changes. 14 young and 9 older adults underwent 5-days of bed rest followed by 8-weeks of lower limb eccentric exercise rehabilitation (REHAB). Dual-energy X-ray absorptiometry, magnetic resonance imaging and myofiber analysis were used to identify muscle morphology and CLIX-IR and CLIX-β were used to assess insulin sensitivity. Skeletal muscle macrophages, CD68 (pan), CD11b (M1), CD163 (M2), CD206 (M2), were characterized using immunohistochemistry and gene expression. Insulin sensitivity, independent of age, decreased ~38% following bed rest and was restored following REHAB. We found robust age-related differences in muscle atrophy during bed rest, yet older and younger adults equally hypertrophied during REHAB. Interestingly, there were age-related differences in macrophage content (CD68 CD11b and CD68 CD11b cells) but both young and old similarly increased macrophages with REHAB. Satellite cell changes during rehab corresponded to macrophage content changes. Muscle tissue resident macrophages and gene expression, were not associated with changes in insulin sensitivity following bed rest and REHAB. These data suggest that muscle macrophages are modulated as a result of exercise rehabilitation following bed rest and may more associated with muscle regrowth/hypertrophy rather than insulin sensitivity in young or older adults. This trial was registered at clinicaltrials.gov as NCT01669590.
MeSH Terms
- Absorptiometry, Photon
- Adolescent
- Adult
- Age Factors
- Aged
- Antigens, CD
- Bed Rest
- Case-Control Studies
- Exercise
- Exercise Therapy
- Female
- Gene Expression
- Humans
- Insulin Resistance
- Macrophages
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Muscle, Skeletal
- Muscular Atrophy
- Prospective Studies
- Young Adult
Keywords
- Aging
- Atrophy
- Eccentric exercise
- Immune cells
- M1
- M2
- Muscle-resident
- Recovery
- Regrowth
- Rehabilitation
- Training
The review describes neuro-immuno-endocrine signal molecules expression in human endometrial cells in the normal conditions, in the pathology and during aging. Human endometrial cells synthesizes estrogen, progesterone, estradiol, progestin, cell adhesion molecules (integrines α1β1, α4β1, αVβ3, L-selectin, Е-catgerin, MUC1), grow factors (TGF, EGF, HB-EGF, IGF), cytokines (IL-1, IL-2, INF-α, IL-12, СХСL10, CXCL11, CXCR3), various immune cells markers (CD68, CD105, CD163, CD16, CD56, CD4, CD8), heat shock proteins (HSP60, HSP70, HSP90, VEGF, MMP). Changes of this molecules expression level are the base of the social significant diseases as endometriosis, endometrial cancer and infertility. Thus, the investigation of neuro-immuno-endocrine interactions in endometrial cells can be used for new drugs creating, in differential diagnostics of endometrial cancer and increasing of extracorporal fertilization success.
MeSH Terms
- Aging
- Biological Factors
- Cellular Senescence
- Cytokines
- Endometrium
- Female
- Heat-Shock Proteins
- Hormones
- Humans
- Signal Transduction
Keywords
- aging
- endometrium
- neuro-immuno-endocrine interactions
- pathology
- signal molecules
In this study, we examined the combined effect of aging and myocardial infarction on left ventricular remodeling, focusing on matrix metalloproteinase (MMP)-9-dependent mechanisms. We enrolled 55 C57BL/6J wild type (WT) and 85 MMP-9 Null (Null) mice of both sexes at 11-36 months of age and evaluated their response at Day 7 post-myocardial infarction. Plasma MMP-9 levels positively linked to age in WT mice (r = .46, p = .001). MMP-9 deletion improved survival (76% for WT vs 88% for Null, p = .021). Post-myocardial infarction, there was a progressive increase in left ventricular dilation with age in WT but not in Null mice. By inflammatory gene array analysis, WT mice showed linear age-dependent increases in three different proinflammatory genes (C3, CCl4, and CX3CL1; all p < .05), whereas Null mice showed increases in three proinflammatory genes (CCL5, CCL9, and CXCL4; all p < .05) and seven anti-inflammatory genes (CCL1, CCL6, CCR1, IL11, IL1r2, IL8rb, and Mif; all p < .05). Compared with WT, macrophages isolated from Null left ventricle infarct demonstrated enhanced expression of anti-inflammatory M2 markers CD163, MRC1, TGF-β1, and YM1 (all p < .05), without affecting proinflammatory M1 markers. In conclusion, MMP-9 deletion stimulated anti-inflammatory polarization of macrophages to attenuate left ventricle dysfunction in the aging post-myocardial infarction.
MeSH Terms
- Aging
- Animals
- Cytokines
- Echocardiography
- Female
- Gene Expression
- Immunohistochemistry
- Ligation
- Male
- Matrix Metalloproteinase 9
- Mice
- Mice, Inbred C57BL
- Myocardial Infarction
- Real-Time Polymerase Chain Reaction
- Survival Analysis
- Ventricular Remodeling
Keywords
- Aging
- Cardiac remodeling
- M2 phenotype.
- Macrophage polarization
It is well documented that the intrinsic enteric nervous system of the gastrointestinal (GI) tract sustains neuronal losses and reorganizes as it ages. In contrast, age-related remodeling of the extrinsic sympathetic projections to the wall of the gut is poorly characterized. The present experiment, therefore, surveyed the sympathetic projections to the aged small intestine for axonopathies. Furthermore, the experiment evaluated the specific prediction that catecholaminergic inputs undergo hyperplastic changes. Jejunal tissue was collected from 3-, 8-, 16-, and 24-month-old male Fischer 344 rats, prepared as whole mounts consisting of the muscularis, and processed immunohistochemically for tyrosine hydroxylase, the enzymatic marker for norepinephrine, and either the protein CD163 or the protein MHCII, both phenotypical markers for macrophages. Four distinctive sympathetic axonopathy profiles occurred in the small intestine of the aged rat: (1) swollen and dystrophic terminals, (2) tangled axons, (3) discrete hyperinnervated loci in the smooth muscle wall, including at the bases of Peyer's patches, and (4) ectopic hyperplastic or hyperinnervating axons in the serosa/subserosal layers. In many cases, the axonopathies occurred at localized and limited foci, involving only a few axon terminals, in a pattern consistent with incidences of focal ischemic, vascular, or traumatic insult. The present observations underscore the complexity of the processes of aging on the neural circuitry of the gut, with age-related GI functional impairments likely reflecting a constellation of adjustments that range from selective neuronal losses, through accumulation of cellular debris, to hyperplasias and hyperinnervation of sympathetic inputs.
MeSH Terms
- Aging
- Animals
- Autonomic Nervous System Diseases
- Enteric Nervous System
- Immunohistochemistry
- Male
- Muscle, Smooth
- Rats
- Rats, Inbred F344
Keywords
- CD163
- Gastrointestinal
- MHCII
- Muscularis
- Myenteric
- Resident macrophages
With age, alpha-synuclein (α-SYNC) misfolds and forms insoluble deposits of protein in the myenteric plexus, leading presumably to dystrophy and degeneration in the circuitry controlling gastrointestinal (GI) function. The present experiment examined aggregates of α-SYNC in the aging small intestine and investigated how macrophages in the wall of the GI tract respond to these aberrant deposits. Groups of adult and aged Fisher 344 rats were studied. Whole mounts of duodenal, jejunal, and ileal smooth muscle wall, including the myenteric plexus, were prepared. Double labeling immunohistochemistry was used to stain α-SYNC protein and the phenotypic macrophage antigens CD163 and MHCII. Alpha-synuclein accumulated in dense aggregates in axons of both postganglionic and preganglionic neurons throughout the small intestine. Staining patterns suggested that deposits of protein occur initially in axonal terminals and then spread retrogradely toward the somata. Macrophages that were adjacent to dystrophic terminal processes were swollen and contained vacuoles filled with insoluble α-SYNC, and these macrophages commonly had the phenotype of alternatively activated phagocytes. The present results suggest that macrophages play an active phagocytotic role in removing α-SYNC aggregates that accumulate with age in the neural circuitry of the gut. Our observations further indicate that this housekeeping response does not clear the protein sufficiently to eliminate all synucleinopathies or their precursor aggregates from the healthy aging GI tract. Thus, accumulating deposits of insoluble α-SYNC in the wall of the GI tract may contribute, especially when compounded by disease or inflammation, to the age-associated neuropathies in the gut that compromise GI function.
MeSH Terms
- Age Factors
- Aging
- Animals
- Antigens, CD
- Antigens, Differentiation, Myelomonocytic
- Autonomic Fibers, Postganglionic
- Autonomic Fibers, Preganglionic
- Biomarkers
- Histocompatibility Antigens Class II
- Immunohistochemistry
- Intestine, Small
- Macrophage Activation
- Macrophages
- Male
- Muscle, Smooth
- Myenteric Plexus
- Phagocytosis
- Phenotype
- Protein Folding
- Rats
- Rats, Inbred F344
- Receptors, Cell Surface
- alpha-Synuclein
Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8( ) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16( ) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16( ) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8( ) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.
MeSH Terms
- Adult
- Age Factors
- Aging
- Antigens, CD
- Antigens, Differentiation, Myelomonocytic
- Biomarkers
- CD8-Positive T-Lymphocytes
- Case-Control Studies
- Chemokine CXCL10
- Cross-Sectional Studies
- Female
- GPI-Linked Proteins
- HIV
- HIV Infections
- Humans
- Immunity, Innate
- Immunophenotyping
- Lipopolysaccharide Receptors
- Middle Aged
- Monocytes
- Neopterin
- Receptors, Cell Surface
- Receptors, IgG
The rhesus macaque (Macaca mulatta) is used extensively in translational biomedical research and drug development studies and is an important model of aging. Macaques often develop myocardial fibrosis with age, which can result in the loss of normal cardiac architecture with the expansion of the extracellular matrix and deposition of collagen. The etiology and pathogenesis of this pernicious process is poorly understood. Cardiac fibrosis was assessed using histologic and immunohistochemical techniques in cardiac tissue sections from 34 rhesus macaques. Overall left ventricular and left ventricular mid-myocardial interstitial/perivascular fibrosis were positively correlated with age (r = .6522, p < .0001 and r = .4704, p = .005, respectively). When divided into young (mean = 2.8 years), middle-aged (mean = 17.5 years), and advanced age (mean = 29.2 years) groups, immunophenotypic characterization of antigen presenting cells revealed differential expression of CD163 and DC-SIGN between the young and middle-aged groups compared to the advanced age group (p < .0001). HAM-56 expression decreased significantly in the advanced age cohort (p = .0021). The expression of CD8, CD163, and DC-SIGN correlated positively with age (r = .3999, p = .0191; r = .5676, p = .0005; r = .5245, p = .0014, respectively). These results show the importance of myocardial fibrosis as a common age-related pathology and additionally, alterations in T cell, macrophage, and dendritic cell phenotype in rhesus macaque myocardium are associated with age but unassociated with the fibrosis.
MeSH Terms
- Aging
- Animals
- Antigens, CD
- Dendritic Cells
- Fibrosis
- Immunohistochemistry
- Immunophenotyping
- Macaca mulatta
- Macrophages
- Myocardium
- Statistics, Nonparametric
- T-Lymphocytes
To compare the impact of HIV infection and healthy ageing on monocyte phenotype and function and determine whether age-related changes induced by HIV are reversed in antiretroviral treated individuals. A cross sectional study of monocyte ageing markers in viremic and virologically suppressed HIV-positive males aged 45 years or less and age-matched and elderly (≥65 years) HIV-uninfected individuals. Age-related changes to monocyte phenotype and function were measured in whole blood assays ex vivo on both CD14( )CD16(-) (CD14( )) and CD14(variable)CD16( ) (CD16( )) subsets. Plasma markers relevant to innate immune activation were measured by ELISA. Monocytes from young viremic HIV-positive males resemble those from elderly controls, and show increased expression of CD11b (P < 0.0001 on CD14( ) and CD16( )subsets) and decreased expression of CD62L and CD115 (P = 0.04 and 0.001, respectively, on CD14( ) monocytes) when compared with young uninfected controls. These changes were also present in young virologically suppressed HIV-positive males. Innate immune activation markers neopterin, soluble CD163 and CXCL10 were elevated in both young viremic (P < 0.0001 for all) and virologically suppressed (P = 0.0005, 0.003 and 0.002, respectively) HIV-positive males with levels in suppressed individuals resembling those observed in elderly controls. Like the elderly, CD14( ) monocytes from young HIV-positive males exhibited impaired phagocytic function (P = 0.007) and telomere-shortening (P = 0.03) as compared with young uninfected controls. HIV infection induces changes to monocyte phenotype and function in young HIV-positive males that mimic those observed in elderly uninfected individuals, suggesting HIV may accelerate age-related changes to monocytes. Importantly, these defects persist in virologically suppressed HIV-positive individuals.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Anti-Retroviral Agents
- Biomarkers
- Cross-Sectional Studies
- Drug Therapy, Combination
- HIV Infections
- Humans
- Male
- Middle Aged
- Monocytes
Macrophages are part of the tumor microenvironment and have been associated with poor prognosis in uveal melanoma. We determined the presence of macrophages and their differentiation status in a murine intraocular melanoma model. Inoculation of B16F10 cells into the anterior chamber of the eye resulted in rapid tumor outgrowth. Strikingly, in aged mice, tumor progression depended on the presence of macrophages, as local depletion of these cells prevented tumor outgrowth, indicating that macrophages in old mice had a strong tumor-promoting role. Immunohistochemistry and gene expression analysis revealed that macrophages carried M2-type characteristics, as shown by CD163 and peroxisome proliferator-activated receptor gamma expression, and that multiple angiogenic genes were heavily overrepresented in tumors of old mice. The M2-type macrophages were also shown to have immunosuppressive features. We conclude that tumor-associated macrophages are directly involved in tumor outgrowth of intraocular melanoma and that macrophages in aged mice have a predisposition for an M2-type profile.
MeSH Terms
- Aging
- Animals
- Cell Line, Tumor
- Cell Polarity
- Cell Proliferation
- Clodronic Acid
- Conjunctiva
- Disease Models, Animal
- Eye Neoplasms
- Growth Inhibitors
- Liposomes
- Macrophages
- Male
- Melanoma, Experimental
- Mice
- Mice, Inbred C57BL
- Neovascularization, Pathologic
Although there has been great progress in the characterization of alphabeta T cell differentiation, selection, and function, gammadelta T cells have remained poorly understood. One of the main reasons for this is the lack of gammadelta T cell-specific surface markers other than the TCR chains themselves. In this study we describe two novel surface receptors, SCART1 and SCART2. SCARTs are related to CD5, CD6, and CD163 scavenger receptors but, unlike them, are found primarily on developing and mature gammadelta T cells. Characterization of SCART2 positive immature and peripheral gammadelta T cells suggests that they undergo lineage specification in the thymus and belong to a new IL-17-producing subset with distinct homing capabilities.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Cell Lineage
- Cell Movement
- Cells
- Cells, Cultured
- Dermis
- Down-Regulation
- Interleukin-17
- Lymph Nodes
- Mice
- Molecular Sequence Data
- Phylogeny
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, Cell Surface
- Sequence Alignment
- Signal Transduction
- Thymus Gland
The aetiology of porcine post-weaning multisystemic wasting syndrome (PMWS) is poorly understood. Porcine circovirus type 2 (PCV-2) is an essential component of the experimental disease model for PMWS: however, evidence from experimental and field studies indicates that additional factors play a critical role in the aetiopathogenesis of PMWS. Current candidates include (1) immune stimulation (for example, via co-infection or vaccination), and (2) a novel infectious agent. A prospective, longitudinal case-control study was designed to investigate molecular triggers in leucocytes of neonatal piglets that may predispose to the development of PMWS. Blood samples were collected weekly from pigs (n=125) within five farms, from 1 week to 8 weeks of age: that is, before the appearance of clinical signs. Four colour flow cytometry was used to investigate changes in subsets of peripheral blood mononuclear cells, using monoclonal antibodies against the following cell associated markers; sIgG, CD3, MHCII dR, CD14, CD4a, CD8a, CD45RC, CD25, SWC3a, SWC8, CD163 and CD45. Sampling and laboratory analysis was supported by monitoring of clinical signs from 1 week to 20 weeks of age, or until disease supervened. At the conclusion of the study, 68 pigs (54%) were classified in Group 1 (no signs of clinical disease), 34 pigs (27%) in Group 2 (signs of clinical disease but not characteristic of PMWS), 17 pigs (14%) in Group 3 (suspect PMWS case) and 5 pigs (4%) in Group 4 (PMWS case). A single case of Porcine Dermatitis and Nephropathy syndrome (PDNS) was also diagnosed. Significant changes with age were demonstrated in clinically normal, neonatal pigs (Group 1), including an increase in B-cells and T-cells, and an increase in the proportion of total T-cells expressing MHCII. Within the T-cell subset, the proportion of CD8( high) CD4(-) T-cells increased, in addition to the proportion of CD4( ) T-cells co-expressing CD8. Of the factors recorded, farm was found to have a highly significant effect on immune system development in the neonate. Comparison of Groups 1 and 4 cases identified significant differences between pigs which remained normal and those which subsequently developed PMWS. Pigs which went on to develop PMWS had a greater proportion of T-cells expressing MHCII in early life, higher mean intensity of expression of MHCII on T-cells, higher mean intensity of expression of MHCII on B cells and higher expression of CD25 on CD45RC(-) T-cells. These findings suggest that lymphocyte activation may be a key early event in the aetiology of PMWS.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Gene Expression Regulation
- Immunity, Cellular
- Major Histocompatibility Complex
- Porcine Postweaning Multisystemic Wasting Syndrome
- Swine
- T-Lymphocyte Subsets