title: Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection.
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.
authors.affiliation: Clinic of Infectious, Diseases Department of Health Sciences, San Paolo Hospital, University of Milan, Via di Rudini' 8, 20142 Milan, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Tincati
authors.affiliation: Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.affiliation: Clinic of Infectious, Diseases Department of Health Sciences, San Paolo Hospital, University of Milan, Via di Rudini' 8, 20142 Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Marchetti
mesh_terms: D018988:Bacterial Translocation / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018450:Disease Progression; D000069196:Gastrointestinal Microbiome / Q000502:physiology; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology
keywords: Gastrointestinal barrier; Microbial translocation; Microbiota; Mucosal immunity