Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocytes and macrophages play a central role in the pathogenesis of human immunodeficiency virus (HIV)-associated dementia. They represent prominent targets for HIV infection and are thought to facilitate viral neuroinvasion and neuroinflammatory processes. However, many aspects regarding monocyte brain recruitment in HIV infection remain undefined. The nonhuman primate model of AIDS is uniquely suited for examination of the role of monocytes in the pathogenesis of AIDS-associated encephalitis. Nevertheless, an approach to monitor cell migration from peripheral blood into the central nervous system (CNS) in primates had been lacking. Here, upon autologous transfer of fluorescein dye-labeled leukocytes, we demonstrate the trafficking of dye-positive monocytes into the choroid plexus stromata and perivascular spaces in the cerebra of rhesus macaques acutely infected with simian immunodeficiency virus between days 12 and 14 postinfection (p.i.). Dye-positive cells that had migrated expressed the monocyte activation marker CD16 and the macrophage marker CD68. Monocyte neuroinvasion coincided with the presence of the virus in brain tissue and cerebrospinal fluid and with the induction of the proinflammatory mediators CXCL9/MIG and CCL2/MCP-1 in the CNS. Prior to neuroinfiltration, plasma viral load levels peaked on day 11 p.i. Furthermore, the numbers of peripheral blood monocytes rapidly increased between days 4 and 8 p.i., and circulating monocytes exhibited increased functional capacity to produce CCL2/MCP-1. Our findings demonstrate acute monocyte brain infiltration in an animal model of AIDS. Such studies facilitate future examinations of the migratory profile of CNS-homing monocytes, the role of monocytes in virus import into the brain, and the disruption of blood-cerebrospinal fluid and blood-brain barrier functions in primates.
 ...
PMID:Neuroinvasion of fluorescein-positive monocytes in acute simian immunodeficiency virus infection. 1771 37

Lymphoid tissues are sites of soluble and cell-associated antigen sampling of peripheral tissues, and they are key compartments for the generation of cellular and humoral immune responses. Hilar lymph nodes (HiLNs), which drain the lungs, were examined to understand the effects of simian immunodeficiency virus (SIV) infection on this compartment of the immune system. Histologic and messenger RNA (mRNA) expression profiling approaches were used to determine the numbers, types, and distributions of SIV viral RNA cells and to identify differentially expressed genes in HiLNs during SIV infection. SIV RNA cells were found to be primarily CD68 and localized to paracortical and medullary regions early in infection, whereas they resided mainly in paracortex during AIDS. As SIV infection progressed, CXCL9, CXCL10, interferon-gamma, and Toll-like receptor 3 levels all increased. In contrast, CCL19 increased early in infection but decreased during AIDS, whereas CCL21 decreased progressively throughout infection. Finally, local levels of cellular activation were increased throughout infection. Taken together, these findings indicate that SIV infection leads to an inflammatory environment in lung-draining lymph nodes that is characterized by type 1 cytokines and chemokines and likely has an impact on the nature and strength of immune responses to pulmonary pathogens.
 ...
PMID:Virologic and immunologic events in hilar lymph nodes during simian immunodeficiency virus infection: development of polarized inflammation. 1797 6

We previously reported that CD4C/human immunodeficiency virus (HIV)(Nef) transgenic (Tg) mice, expressing Nef in CD4(+) T cells and cells of the macrophage/dendritic cell (DC) lineage, develop a severe AIDS-like disease, characterized by depletion of CD4(+) T cells, as well as lung, heart, and kidney diseases. In order to determine the contribution of distinct populations of hematopoietic cells to the development of this AIDS-like disease, five additional Tg strains expressing Nef through restricted cell-specific regulatory elements were generated. These Tg strains express Nef in CD4(+) T cells, DCs, and macrophages (CD4E/HIV(Nef)); in CD4(+) T cells and DCs (mCD4/HIV(Nef) and CD4F/HIV(Nef)); in macrophages and DCs (CD68/HIV(Nef)); or mainly in DCs (CD11c/HIV(Nef)). None of these Tg strains developed significant lung and kidney diseases, suggesting the existence of as-yet-unidentified Nef-expressing cell subset(s) that are responsible for inducing organ disease in CD4C/HIV(Nef) Tg mice. Mice from all five strains developed persistent oral carriage of Candida albicans, suggesting an impaired immune function. Only strains expressing Nef in CD4(+) T cells showed CD4(+) T-cell depletion, activation, and apoptosis. These results demonstrate that expression of Nef in CD4(+) T cells is the primary determinant of their depletion. Therefore, the pattern of Nef expression in specific cell population(s) largely determines the nature of the resulting pathological changes.
 ...
PMID:Selective expression of human immunodeficiency virus Nef in specific immune cell populations of transgenic mice is associated with distinct AIDS-like phenotypes. 1960 70

Cells infected with the human immunodeficiency virus (HIV) can fuse with CD4(+) cells leading to the formation of multinucleated cells. The presence of multinucleated cells infected with HIV in tissues of patients has been documented, although their cellular composition and role in AIDS pathogenesis is still under study. Here, we present evidence of in vitro heterotypic lymphocyte-monocyte fusion in cocultures of lymphocytic Jurkat T cells expressing the HIV-1 gp120/gp41 glycoproteins (Env) and CD4(+) monocytic THP-1 cells. Using a previously characterized method that involves differential labeling of fusion partners with fluorescent probes and flow cytometry analysis after coculture, up to 20% of double fluorescent cells were detected in 48h. This double fluorescent cell population was produced by heterotypic lymphocyte-monocyte fusion as it was not observed when Jurkat T cells expressing a mutant non-fusogenic Env protein were used. Heterokaryon formation was inhibited by an anti-CD4 monoclonal antibody and the HIV-fusion inhibitor peptide T-20. About 68% of heterokaryons remained alive and non-apoptotic after 2days of coculture. In heterokaryons, CD4 was barely detectable and the expression of the CD3 and CD28 lymphoid markers was greatly reduced, whereas the expression of CD32 and the intracellular antigen CD68, both markers of monocytic cells, remained unchanged. In contrast with unfused T cells, heterokaryons only expressed very low levels of the lymphoid activation marker CD25 following treatment with PMA plus ionomycin. These studies point to the possible generation of lymphocyte-monocyte heterokaryons with a myeloid phenotype during HIV infection, with unknown consequences for AIDS pathogenesis.
 ...
PMID:Quantitative and phenotypic analyses of lymphocyte-monocyte heterokaryons induced by the HIV envelope proteins: Significant loss of lymphoid markers. 2111 Sep 55

The objective of this study is to assess the relationship between protozoa in spontaneously expectorated sputum samples and a range of clinical and immunological variables. Clinical details including age, gender, smoking status, and use of oral or inhaled steroids were recorded for a cohort of 199 patients whose spontaneously expectorated sputum samples were submitted to a Cytology Laboratory in Spain between January 2005 and December 2006. Slides were scanned for protozoa under light microscopy and scanned for monocytes/small macrophages highlighted by immunocytochemistry (CD68 monoclonal antibody). One hundred ninety-one patients provided adequate sputum samples, of whom 70 had protozoa in their sputum. There was a strong relationship between the presence of protozoa and monocytes/small macrophages identified under light microscopy (P < 0.001). A binary logistic regression model also indicated a relationship between protozoa and both smoking status and steroid use. The diagnoses in those with protozoa included infection (including tuberculosis), chronic obstructive pulmonary disease (COPD), lung fibrosis, asthma, chronic liver disease, immunosuppression, cancer, pancreatic or renal disease, heart failure, and AIDS. The identified association between protozoa and monocytes/small macrophages in sputum suggests an immune response and warrants further investigation to clarify whether or not these organisms have any pathological significance in this wide range of conditions.
 ...
PMID:Clinical and immunological characteristics associated with the presence of protozoa in sputum smears. 2168 74

HIV-associated sensory neuropathy (HIV-SN) is currently the most common neurological complication of chronic HIV infection and continues to substantially affect patient quality of life. Mechanisms underlying the neuronal damage and loss observed in sensory ganglia of HIV-infected individuals have not been sufficiently studied. The present study aimed to develop and characterize a model of HIV-SN using SIV-infected CD8 T-lymphocyte-depleted rhesus macaques (Macaca mulatta). Uninfected controls (n = 5), SIV-infected CD8-depleted (n = 4), and SIV-infected non-CD8-depleted (n = 6) animals were used. Of the six non-CD8-depleted animals, three were conventional progressors (progressing to AIDS >1 year after infection) and three were rapid progressors (AIDS within 6 months). Dorsal root ganglia (DRG) were examined for histological hallmarks of HIV-SN, including satellitosis, presence of Nageotte nodules, and neuronophagia, as well as increased numbers of CD68(+) macrophages and abundant viral replication. In contrast to non-CD8-depleted animals, which had mild to moderate DRG pathology, the CD8-depleted SIV-infected animals had moderate to severe DRG damage, with increased numbers of CD68(+) satellite cells. Additionally, there was marked active viral replication in the affected DRG. These findings confirm that many features of HIV-SN can be recapitulated in the CD8-depleted SIV-infected rhesus macaque model within a short time frame and illustrate the importance of this model for study of sensory neuropathy.
 ...
PMID:Dorsal root ganglia damage in SIV-infected rhesus macaques: an animal model of HIV-induced sensory neuropathy. 2232 98

The relationship between exogenous contraceptive hormones and permissiveness of the female genital tract to human immunodeficiency virus type 1 (HIV-1) is the subject of renewed debate. To better characterize the effect of depot medroxyprogesterone acetate (DMPA) on HIV-1 cellular targets and epithelial integrity in the vagina, we compared leukocyte populations, markers of activation and proliferation, and the density of intercellular junctional proteins in the vaginal epithelium of women during the follicular and luteal phases of the menstrual cycle and approximately 12 weeks after receiving a DMPA injection. This prospective cohort study involved 15 healthy women. Vaginal biopsies were obtained in the follicular and luteal phases of the menstrual cycle, and approximately 12 weeks following a 150-mg intramuscular injection of DMPA. Leukocyte populations, activation phenotype, and epithelial tight junction and adherens proteins were evaluated by immunohistochemistry. After receiving DMPA, the numbers of CD45, CD3, CD8, CD68, HLA-DR, and CCR5 bearing immune cells were significantly (p<0.05) increased in vaginal tissues, compared to the follicular and/or luteal phases of untreated cycles. There were no significant differences in immune cell populations between the follicular and luteal phases of the control cycle. There were also no statistically significant differences in epithelial thickness and density of epithelial tight junction and adherens proteins among the follicular, luteal, and post-DMPA treatment sampling points. In this pilot study, vaginal immune cell populations were significantly altered by exogenous progesterone, resulting in increased numbers of T cells, macrophages, and HLA-DR- and CCR5-positive cells.
AIDS Res Hum Retroviruses 2013 Mar
PMID:Depot medroxyprogesterone acetate increases immune cell numbers and activation markers in human vaginal mucosal tissues. 2318 32

Abstract LYVE-1 is a marker expressed by lymphatic endothelial cells (LECs) that line the lymphatic endothelium. Through studies designed to examine potential changes in expression of LYVE-1 in cynomolgus macaque colon tissues during the course of simian immunodeficiency virus (SIV) infection, we discovered that LYVE-1 was expressed by heterogenous populations of cells. As revealed by in situ hybridization (ISH), LYVE-1 mRNA levels in colon were decreased in macaques with AIDS compared with acutely infected or uninfected macaques. In the submucosal layer of the colon, approximately half of the LYVE-1-expressing cells co-expressed the dendritic cell (DC) marker, DC-SIGN/CD209, and this percentage did not change appreciably during infection. Subsets of cells expressing LYVE-1 also co-expressed macrophage markers, such as CD68 and the macrophage mannose receptor (MMR)/CD206, in both the colon and lymph nodes. LECs, DCs, and macrophages that co-expressed LYVE-1 were observed in colon and lymph node from uninfected, healthy animals as well as in tissues with SIV-driven inflammation. These findings provide further definition of the phenotypic overlap between LECs and antigen presenting cells, reveal the heterogeneity within the population of cells expressing the lymphatic marker LYVE-1, and show that SIV modulates this population of cells in a mucosal surface across which the virus is acquired.
 ...
PMID:Characterization of cells expressing lymphatic marker LYVE-1 in macaque large intestine during simian immunodeficiency virus infection identifies a large population of nonvascular LYVE-1(+)/DC-SIGN(+) cells. 2353 Nov 82

To understand the pathogenicity of acquired immune deficiency syndrome (AIDS), it is important to clarify where, when and how the virus replicates in the body of infected individuals. To identify the major virus replication site at the end stage of SHIV infection, we investigated the systemic tissues of SHIV-infected monkeys that developed AIDS-like disease. We quantified proviral DNA, and compared the mutation patterns of the viruses in various systemic tissues and in peripheral blood through phylogenetic analysis of the full genome sequence. We found that the amounts of proviral DNA detected in internal tissues were higher than those in peripheral blood mononuclear cells. In the sequence and phylogenetic tree analyses, the mutation patterns of the viruses in each tissue were generally different. However, the mutation pattern of the viruses in the jejunum and mesenteric lymph node were most similar to that of plasma viral RNA among the tissues examined in all three monkeys. In two of the three monkeys, which were euthanized earlier, viruses in the jejunum and mesenteric lymph node occupied the root position of the phylogenetic tree. Furthermore, in these tissues, more than 50% of SHIV-expressing cells were identified as macrophages based on co-expression of CD68. These results suggest that macrophages of the small intestine and/or mesenteric lymph node are the major virus production site at the end stage of SHIV infection of macaques.
...
PMID:Genetic similarity of circulating and small intestinal virus at the end stage of acute pathogenic simian-human immunodeficiency virus infection. 2388 55

A common route for HIV-1 infection is sexual transmission across colorectal mucosa, which is thought to be 10-2,000 times more vulnerable to infection than that of the female genital tract. Mucosal surfaces are the first line of defense against many pathogens but the antigen-presenting cells (APCs), key regulators of innate immunity and determinants of adaptive immunity, are not well defined in these target tissues. Using immunohistochemistry, dendritic cells expressing Langerin (CD207(+)), a lectin known to bind and internalize HIV-1, were detected in the periphery of colonic glands and sparsely scattered in the submucosa similarly in colorectal mucosa. This cell type, well known in skin, has generally not been reported in colonic/rectal mucosa. Unexpectedly, the largest APC population observed was a macrophage-like population expressing the well-characterized tissue macrophage markers CD68 and CD163. Confocal microscopy of these cells revealed colocalization of CD209 (DC-SIGN), a presumed dendritic cell marker believed to facilitate HIV-1 transmission, but not other dendritic cell markers. These results show evidence of the unconfirmed presence of Langerhans cells in colorectal mucosa and a predominance of macrophage-like APCs that express CD209 (DC-SIGN). These findings define potential target cells in the pathogenesis of HIV-1 transmission, which may have key implications for the study of early transmission events in normal colorectal mucosa, as well as other infectious diseases and primary immune diseases involving the gut.
AIDS Res Hum Retroviruses 2014 Mar
PMID:Antigen-presenting cell candidates for HIV-1 transmission in human distal colonic mucosa defined by CD207 dendritic cells and CD209 macrophages. 2413 15


<< Previous 1 2 3 4 5 6 Next >>