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Cell Rep. 2015 Nov 24;13(8):1589-97. doi: 10.1016/j.celrep.2015.10.026. Epub 2015 Nov 12.

Gut-Resident Lactobacillus Abundance Associates with IDO1 Inhibition and Th17 Dynamics in SIV-Infected Macaques.

Author information

1
Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
2
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.
3
Laboratory of Molecular Microbiology, Program in Tissue Immunity and Repair and Immunopathogenesis Section, NIAID, NIH, Bethesda, MD 20892, USA.
4
Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA.
5
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
6
Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
7
Department of Medicine, Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
8
Department of Pharmaceutics, University of Washington, Seattle, WA 98121, USA.
9
Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: susan.lynch@ucsf.edu.
10
Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: mike.mccune@ucsf.edu.

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.

PMID:
26586432
PMCID:
PMC4782968
DOI:
10.1016/j.celrep.2015.10.026
[Indexed for MEDLINE]
Free PMC Article

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