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 Klatt, Jason M. Brenchley, Susan V. Lynch, Joseph M. McCune

Research output: Contribution to journalArticle

44 Scopus citations

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. Vujkovic-Cvijin et al. show that fecal Lactobacillus associates with control of the immunomodulatory indoleamine 2,3-dioxygenase (IDO) pathway, providing a link between the gut microbiome and mucosal immune homeostasis in the pathogenesis of SIV disease.

Original languageEnglish (US)
Pages (from-to)1589-1597
Number of pages9
JournalCell Reports
Volume13
Issue number8
DOIs
StatePublished - Nov 24 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Vujkovic-Cvijin, I., Swainson, L. A., Chu, S. N., Ortiz, A. M., Santee, C. A., Petriello, A., Dunham, R. M., Fadrosh, D. W., Lin, D. L., Faruqi, A. A., Huang, Y., Apetrei, C., Pandrea, I., Hecht, F. M., Pilcher, C. D., Klatt, N., Brenchley, J. M., Lynch, S. V., & McCune, J. M. (2015). Gut-Resident Lactobacillus Abundance Associates with IDO1 Inhibition and Th17 Dynamics in SIV-Infected Macaques. Cell Reports, 13(8), 1589-1597. https://doi.org/10.1016/j.celrep.2015.10.026