IL-10 impairs local immune response in lung granulomas and lymph nodes during early mycobacterium tuberculosis infection

Eileen A. Wong, Stephanie Evans, Carolyn R. Kraus, Kathleen D. Engelman, Pauline Maiello, Walter J. Flores, Anthony M. Cadena, Edwin Klein, Kayla Thomas, Alexander G. White, Chelsea Causgrove, Brianne Stein, Jaime Tomko, Joshua T. Mattila, Hannah Gideon, P. Ling Lin, Keith A. Reimann, Denise E. Kirschner, Jo Anne L. Flynn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a major global health problem. Lung granulomas are organized structures of host immune cells that function to contain the bacteria. Cytokine expression is a critical component of the protective immune response, but inappropriate cytokine expression can exacerbate TB. Although the importance of proinflammatory cytokines in controlling M. tuberculosis infection has been established, the effects of anti-inflammatory cytokines, such as IL-10, in TB are less well understood. To investigate the role of IL-10, we used an Ab to neutralize IL-10 in cynomolgus macaques during M. tuberculosis infection. Anti-IL-10-treated nonhuman primates had similar overall disease outcomes compared with untreated control nonhuman primates, but there were immunological changes in granulomas and lymph nodes from anti-IL-10- treated animals. There was less thoracic inflammation and increased cytokine production in lung granulomas and lymph nodes from IL-10-neutralized animals at 3-4 wk postinfection compared with control animals. At 8 wk postinfection, lung granulomas from IL-10-neutralized animals had reduced cytokine production but increased fibrosis relative to control animals. Although these immunological changes did not affect the overall disease burden during the first 8 wk of infection, we paired computational modeling to explore late infection dynamics. Our findings support that early changes occurring in the absence of IL-10 may lead to better bacterial control later during infection. These unique datasets provide insight into the contribution of IL-10 to the immunological balance necessary for granulomas to control bacterial burden and disease pathology in M. tuberculosis infection.

Original languageEnglish
Pages (from-to)644-659
Number of pages16
JournalJournal of Immunology
Volume204
Issue number3
DOIs
Publication statusPublished - 1 Feb 2020
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) R01AI123093 and R01HL110811 (awarded to D.E.K. and J.L.F.). Any simulations also use resources of the National Energy Research Scientific Computing Center, which is supported by

Funding Information:
the Office of Science of the U.S. Department of Energy under Contract ACI-1053575, and the Extreme Science and Engineering Discovery Environment, which is supported by National Science Foundation Grant MCB140228. E.A.W. was supported by NIH T32 AI060525, and S.E. was supported by an Intersect Fellowship from the American Association of Immunologists.

Publisher Copyright:
© 2020 by The American Association of Immunologists, Inc.

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