title: Gut-Resident Lactobacillus Abundance Associates with IDO1 Inhibition and Th17 Dynamics in SIV-Infected Macaques.
abstract: Gut microbes can profoundly modulate mucosal barrier-promoting Th17 cells in mammals. A salient feature of HIV/simian immunodeficiency virus (SIV) immunopathogenesis is the loss of Th17 cells, which has been linked to increased activity of the immunomodulatory enzyme, indoleamine 2,3-dioxygenase 1 (IDO 1). The role of gut microbes in this system remains unknown, and the SIV-infected rhesus macaque provides a well-described model for HIV-associated Th17 loss and mucosal immune disruption. We observed a specific depletion of gut-resident Lactobacillus during acute and chronic SIV infection of rhesus macaques, which was also seen in early HIV-infected humans. This depletion in rhesus macaques correlated with increased IDO1 activity and Th17 loss. Macaques supplemented with a Lactobacillus-containing probiotic exhibited decreased IDO1 activity during chronic SIV infection. We propose that Lactobacillus species inhibit mammalian IDO1 and thus may help to preserve Th17 cells during pathogenic SIV infection, providing support for Lactobacillus species as modulators of mucosal immune homeostasis.
authors.affiliation: Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Vujkovic-Cvijin
authors.affiliation: Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Swainson
authors.affiliation: Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; University of California, Berkeley-University of California, San Francisco Joint Medical Program, San Francisco, CA 94143, USA.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Chu
authors.affiliation: Laboratory of Molecular Microbiology, Program in Tissue Immunity and Repair and Immunopathogenesis Section, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Ortiz
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Clark A
authors.initials: CA
authors.lastname: Santee
authors.affiliation: Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Annalise
authors.initials: A
authors.lastname: Petriello
authors.affiliation: Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Dunham
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Fadrosh
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Din L
authors.initials: DL
authors.lastname: Lin
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Faruqi
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Apetrei
authors.affiliation: Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Ivona
authors.initials: I
authors.lastname: Pandrea
authors.affiliation: Department of Medicine, Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.affiliation: Department of Medicine, Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pilcher
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, WA 98121, USA.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.affiliation: Laboratory of Molecular Microbiology, Program in Tissue Immunity and Repair and Immunopathogenesis Section, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: susan.lynch@ucsf.edu.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
authors.affiliation: Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: mike.mccune@ucsf.edu.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
mesh_terms: D000818:Animals; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000382:microbiology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D007778:Lactobacillus / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000382:microbiology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase