title: Bacteroides are associated with GALT iNKT cell function and reduction of microbial translocation in HIV-1 infection.
abstract: Invariant natural killer T (iNKT) cells are innate-like T cells that respond to lipid antigens presented by CD1d. These immunoregulatory cells have the capacity for rapid cytokine release after antigen recognition and are essential for the activation of multiple arms of the immune response. HIV-1 infection is associated with iNKT cell depletion in the peripheral blood; however, their role in the gastrointestinal-associated lymphoid tissue (GALT) is less well studied. Our results show that iNKT cells are found at a higher frequency in GALT compared with blood, particularly in HIV-1 elite controllers. The capacity of iNKT cells to produce interleukin-4 (IL-4) and IL-10 in the GALT was associated with less immune activation and lower markers of microbial translocation, whereas regulatory T cell frequency showed positive associations with immune activation. We hypothesized that the composition of the microbiota would influence iNKT cell frequency and function. We found positive associations between the abundance of several Bacteroides species and iNKT cell frequency and their capacity to produce IL-4 in the GALT but not in the blood. Overall, our results are consistent with the hypothesis that GALT iNKT cells, influenced by certain bacterial species, may have a key role in regulating immune activation in HIV-1 infection.
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, District of Columbia, USA.
authors.forename: D
authors.initials: D
authors.lastname: Paquin-Proulx
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ching
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: I
authors.initials: I
authors.lastname: Vujkovic-Cvijin
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: D
authors.initials: D
authors.lastname: Fadrosh
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: L
authors.initials: L
authors.lastname: Loh
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, School of Pharmacy University of California, San Francisco, California, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Somsouk
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Lynch
authors.affiliation: HIV/AIDS Division, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Hunt
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, District of Columbia, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Nixon
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: D
authors.initials: D
authors.lastname: SenGupta
mesh_terms: D000328:Adult; D000368:Aged; D055610:Antigens, CD1d / Q000378:metabolism; D001439:Bacteroides / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D008055:Lipids / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D055610:Antigens, CD1d; D008055:Lipids; D016753:Interleukin-10; D015847:Interleukin-4