Infected cells and immune cells in the gastrointestinal tract of AIDS patients. An immunohistochemical study of 127 cases

Jarry, Anne; Cortez, Alane Pereira; René, E; Muzeau, Françoise; Brousse, Nicole

doi:10.1111/j.1365-2559.1990.tb01081.x

Cited by 96 publications

(21 citation statements)

References 20 publications

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“…Increased migration into the gut was accompanied by a 4-to 16-fold increase in the secretion of proinflammatory cytokines/chemokines like IL-1␤, CCL5, CXCL9, and CXCL10. Jarry et al (49) showed that the densities of CD68 ϩ and CD11cϩ macrophages were significantly increased in the duodenum of HIV-infected patients.…”

Section: The Gut Macrophage Reservoir In Hiv Infectionmentioning

confidence: 99%

Gastrointestinal Tract and the Mucosal Macrophage Reservoir in HIV Infection

Brown¹,

Mattapallil²

2014

Clin. Vaccine Immunol.

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The gastrointestinal tract (GIT) is a primary site for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection, replication, and dissemination. After an initial explosive phase of infection, HIV establishes latency. In addition to CD4 T cells, macrophages are readily infected, which can persist for long periods of time. Though macrophages at various systemic sites are infected, those present in the GIT constitute a major cellular reservoir due to the abundance of these cells at mucosal sites. Here, we review some of the important findings regarding what is known about the macrophage reservoir in the gut and explore potential approaches being pursued in the field to reduce this reservoir. The development of strategies that can lead to a functional cure will need to incorporate approaches that can eradicate the macrophage reservoir in the GIT. Macrophages are one of the most abundant immune cells in the gut (1, 2). Morphologically, gut macrophages are similar to most resident tissue macrophages, with a mononuclear shape and a granular cytoplasm, and they are highly phagocytic and microbicidal (3-5). They express major histocompatibility complex (MHC) class II, CD36, CD68, CD163 (6, 7), and CD209 (7) but have low levels of CD80, CD86, and CD40 (8-11). Unlike monocytes in peripheral blood that are largely CD14 ϩ , human mucosal macrophages in the gut have been shown to express aϪ phenotype (12, 13). The expression of CD4 and CCR5/CXCR4 key receptors for human immunodeficiency virus (HIV) infection, on macrophage populations has been shown to differ based on the sites the cells reside in. Shen et al. (14) showed that vaginal macrophages expressed CD4 and CCR5/CXCR4 similarly to blood monocytes, whereas intestinal macrophages expressed little or no detectable CD4 and CCR5/CXCR4 (15-17).Interestingly, under normal conditions or in response to Tolllike receptor (TLR) ligands, gut macrophages constitutively secrete anti-inflammatory cytokines, such as interleukin-10 (IL-10), rather than proinflammatory mediators, such as IL-12, IL-23, tumor necrosis factor alpha (TNF-␣), IL-1, IL-6, and interferoninducible protein 10 (IP-10) (18)(19)(20)(21)(22), suggesting that intestinal macrophages may be critical for maintaining immune homeostasis in the gastrointestinal tract (6). Smythies et al. (23) reported that intestinal macrophages displayed significant inflammation anergy even though they had avid phagocytic and bactericidal activity. Depletion of mucosal macrophages was shown to be associated with increased susceptibility to colitis and graft-versus-host disease in mice (24-26). Likewise, altering the phenotype of macrophages to that of a proinflammatory phenotype as seen during HIV replication was associated with increased inflammation and tissue damage (27).In addition to their role in maintaining mucosal immune homeostasis, gut macrophages, like dendritic cells (DC), have been shown to sample microbes directly from the intestinal lumen and transfer these antigens to DC for processing or tran...

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Section: The Gut Macrophage Reservoir In Hiv Infectionmentioning

confidence: 99%

Gastrointestinal Tract and the Mucosal Macrophage Reservoir in HIV Infection

Brown¹,

Mattapallil²

2014

Clin. Vaccine Immunol.

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“…Early after acquisition of HIV/SIV, nearly all CD4 + T-cells in the lamina propria are infected and depleted, and is associated with profound systemic inflammation due to destruction of gut barrier function. 1,[6][7][8][9][10] While combined antiretroviral therapy has dramatically reduced opportunistic infections and…”

Section: -3mentioning

confidence: 99%

Evaluation of oral serum-derived bovine immunoglobulins in HIV-infected patients with chronic idiopathic diarrhea

Asmuth

Hinkle²,

LaMarca

et al. 2017

HIV Clinical Trials

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“…As such, these cells both directly kill foreign pathogens and secrete cytokines in response to infection to activate other cells of the host immune system. These cells are primarily located in tissues where HIV-1 exposure and replication can occur (e.g., the gastrointestinal tract, female genital tract, lymphoid tissues, and brain) [172][173][174][175][176][177]. While HIV-1 is widely known to infect human CD4 + T cells, it can also efficiently infect macrophages in vitro and in vivo.…”

Section: Hiv-1 Infectivity In Macrophagesmentioning

confidence: 99%

Identification of HIV Inhibitors Guided by Free Energy Perturbation Calculations

Acevedo¹,

Ambrose²,

Flaherty³

et al. 2012

curr drug metab

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Free energy perturbation (FEP) theory coupled to molecular dynamics (MD) or Monte Carlo (MC) statistical mechanics offers a theoretically precise method for determining the free energy differences of related biological inhibitors. Traditionally requiring extensive computational resources and expertise, it is only recently that its impact is being felt in drug discovery. A review of computer-aided anti-HIV efforts employing FEP calculations is provided here that describes early and recent successes in the design of human immunodeficiency virus type 1 (HIV-1) protease and non-nucleoside reverse transcriptase inhibitors. In addition, our ongoing work developing and optimizing leads for small molecule inhibitors of cyclophilin A (CypA) is highlighted as an update on the current capabilities of the field. CypA has been shown to aid HIV-1 replication by catalyzing the cis/trans isomerization of a conserved Gly-Pro motif in the Nterminal domain of HIV-1 capsid (CA) protein. In the absence of a functional CypA, e.g., by the addition of an inhibitor such as cyclosporine A (CsA), HIV-1 has reduced infectivity. Our simulations of acylurea-based and 1-indanylketone-based CypA inhibitors have determined that their nanomolar and micromolar binding affinities, respectively, are tied to their ability to stabilize Arg55 and Asn102. A structurally novel 1-(2,6-dichlorobenzamido) indole core was proposed to maximize these interactions. FEP-guided optimization, experimental synthesis, and biological testing of lead compounds for toxicity and inhibition of wild-type HIV-1 and CA mutants have demonstrated a dose-dependent inhibition of HIV-1 infection in two cell lines. While the inhibition is modest compared to CsA, the results are encouraging.

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Infected cells and immune cells in the gastrointestinal tract of AIDS patients. An immunohistochemical study of 127 cases

Cited by 96 publications

References 20 publications

Gastrointestinal Tract and the Mucosal Macrophage Reservoir in HIV Infection

Gastrointestinal Tract and the Mucosal Macrophage Reservoir in HIV Infection

Evaluation of oral serum-derived bovine immunoglobulins in HIV-infected patients with chronic idiopathic diarrhea

Identification of HIV Inhibitors Guided by Free Energy Perturbation Calculations

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