title: Reversing Gut Damage in HIV Infection: Using Non-Human Primate Models to Instruct Clinical Research.
abstract: Antiretroviral therapy (ART) has led to dramatic improvements in the lives of HIV-infected persons. However, residual immune activation, which persists despite ART, is associated with increased risk of non-AIDS morbidities. Accumulating evidence shows that disruption of the gut mucosal epithelium during SIV/HIV infections allows translocation of microbial products into the circulation, triggering immune activation. This disruption is due to immune, structural and microbial alterations. In this review, we highlighted the key findings of gut mucosa studies of SIV-infected macaques and HIV-infected humans that have revealed virus-induced changes of intestinal CD4, CD8 T cells, innate lymphoid cells, myeloid cells, and of the local cytokine/chemokine network in addition to epithelial injuries. We review the interplay between the host immune response and the intestinal microbiota, which also impacts disease progression. Collectively, these studies have instructed clinical research on early ART initiation, modifiers of microbiota composition, and recombinant cytokines for restoring gut barrier integrity.
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Ponte
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Vikram
authors.initials: V
authors.lastname: Mehraj
authors.affiliation: Division of Hematology, McGill University Health Centre, Montreal, Quebec, Canada; Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Ghali
authors.affiliation: INSERM, U1016, Institut Cochin, Paris 75014, France; CNRS, UMR8104, Paris 75014, France; Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France; Université Paris Diderot, Paris 75013, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Couëdel-Courteille
authors.affiliation: INSERM, U1016, Institut Cochin, Paris 75014, France; CNRS, UMR8104, Paris 75014, France; Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Cheynier
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada; Division of Hematology, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007113:Immunity, Innate; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D008251:Macaca; D064307:Microbiota
keywords: Gut barrier integrity; HIV; Interleukin-21; Interleukin-7; Microbial translocation; SIV