Gut-Resident Lactobacillus Abundance Associates with IDO1 Inhibition and Th17 Dynamics in SIV-Infected Macaques
Ivan Vujkovic-Cvijin,
Louise A. Swainson,
Simon N. Chu,
Alexandra M. Ortiz,
Clark A. Santee,
Annalise Petriello,
Richard M. Dunham,
Douglas W. Fadrosh,
Din L. Lin,
Ali A. Faruqi,
Yong Huang,
Cristian Apetrei,
Ivona Pandrea,
Frederick M. Hecht,
Christopher D. Pilcher,
Nichole R. Klatt,
Jason M. Brenchley,
Susan V. Lynch,
Joseph M. McCune
Affiliations
Ivan Vujkovic-Cvijin
Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Louise A. Swainson
Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Simon N. Chu
Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Alexandra M. Ortiz
Laboratory of Molecular Microbiology, Program in Tissue Immunity and Repair and Immunopathogenesis Section, NIAID, NIH, Bethesda, MD 20892, USA
Clark A. Santee
Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA
Annalise Petriello
Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Richard M. Dunham
Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Douglas W. Fadrosh
Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA
Din L. Lin
Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA
Ali A. Faruqi
Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA
Yong Huang
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA
Cristian Apetrei
Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA
Ivona Pandrea
Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA
Frederick M. Hecht
Department of Medicine, Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Christopher D. Pilcher
Department of Medicine, Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Nichole R. Klatt
Department of Pharmaceutics, University of Washington, Seattle, WA 98121, USA
Jason M. Brenchley
Laboratory of Molecular Microbiology, Program in Tissue Immunity and Repair and Immunopathogenesis Section, NIAID, NIH, Bethesda, MD 20892, USA
Susan V. Lynch
Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA
Joseph M. McCune
Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
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.
