Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Apr 11:13:19.
doi: 10.1186/s12981-016-0103-1. eCollection 2016.

Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection

Camilla Tincati  1 , Daniel C Douek  2 , Giulia Marchetti  1
Affiliations
Review

Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection

Camilla Tincati et al. AIDS Res Ther. .

Abstract

Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies. Results from studies addressing the pathogenesis of microbial translocation have improved our knowledge of the damage of the gastrointestinal epithelial barrier occurring in HIV infection. However, the extent to which mucosal impairment translates directly to increased gastrointestinal permeability remains an open issue. In this respect, novel work has established a role for IL-17 and IL-22-secreting T cell populations in limiting microbial translocation and systemic T-cell activation/inflammation, thus representing a possible target of immune-therapeutic interventions shown to be promising in the animal model. Further, recent reports have not only confirmed the presence of a dysbiotic intestinal community in the course of HIV infection but have also shown that it may be linked to mucosal damage, microbial translocation and peripheral immune activation. Importantly, technical advances have also shed light on the metabolic activity of gut microbes, highlighting the need for novel therapeutic approaches to correct the function, as well as the composition, of the gastrointestinal microbiota.

Keywords: Gastrointestinal barrier; Microbial translocation; Microbiota; Mucosal immunity.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
The continuum of gastrointestinal abnormalities in treated and untreated HIV disease. In HIV-negative individuals, a highly diversified microbiota resides in the gut lumen and is shielded from the lamina propria, thus preventing the translocation of bacteria and microbial products to the peripheral blood. Microbial translocation is blocked thanks to the structural integrity of the epithelial barrier and function of gut-resident immune cells, e.g. IL-17- and IL-22- producing cells. In the acute phase of HIV disease, no significant alterations of luminal bacteria and epithelial barrier have been reported. Indeed, markers of microbial translocation (LPS, peptidoglycan, EndoCAb, sCD14, 16S rDNA) and enterocyte damage (I-FABP, sST2) were not detected in plasma samples of acutely-infected individuals and both mucosal and peripheral Th17 cells were only slightly decreased in the earliest phases of HIV infection. Following 6 months from infection (early HIV infection), however, a rise in parameters of microbial translocation and gut impairment was measured in peripheral blood, suggesting initial disruption of mucosal integrity. In the chronic stages of untreated HIV disease, new research studies have demonstrated profound alterations of the intestinal epithelium, with marked impairment of proteins forming the gut junctional complex (JC; cadherin, claudins, zonula occludens 1) which can be found in the peripheral blood. These anatomical alterations are accompanied by changes in the composition and function of the gut microbiota as well as the reduction of IL-17- and IL-22-secreting cell numbers, allowing for the translocation of pathogenic bacteria. Combination antiretroviral therapy (cART) is able to correct gut abnormalities only in part. Persistent defects in JC protein expression, microbial composition and immune function have in fact been described in aviremic individuals. Importantly, these defects appear to be differentially expressed according to the degree of CD4+ T-cell recovery on cART
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Liu Z, Hultin LE, Cumberland WG, et al. Elevated relative fluorescence intensity of CD38 antigen expression on CD8 + T cells is a marker of poor prognosis in HIV infection: results of 6 years of follow-up. Cytometry. 1996;26:1–7. doi: 10.1002/(SICI)1097-0320(19960315)26:1<1::AID-CYTO1>3.0.CO;2-L. - DOI - PubMed
    1. Giorgi JV, Hultin LE, McKeating JA, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis. 1999;179:859–870. doi: 10.1086/314660. - DOI - PubMed
    1. Deeks SG, Kitchen CM, Liu L, et al. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood. 2004;104:942–947. doi: 10.1182/blood-2003-09-3333. - DOI - PubMed
    1. Marchetti G, Bellistrì GM, Borghi E, et al. Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long-term highly active antiretroviral therapy. AIDS. 2008;22:2035–2038. doi: 10.1097/QAD.0b013e3283112d29. - DOI - PubMed
    1. Estes JD, Harris LD, Klatt NR, et al. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog. 2010;6:e1001052. doi: 10.1371/journal.ppat.1001052. - DOI - PMC - PubMed

Publication types

MeSH terms