Reference Database

IL-10 Impairs Local Immune Response in Lung Granulomas and Lymph Nodes during Early Mycobacterium tuberculosis Infection.
Wong, Eileen A
Evans, Stephanie
Kraus, Carolyn R
Engelman, Kathleen D
Maiello, Pauline
Flores, Walter J
Cadena, Anthony M
Klein, Edwin
Thomas, Kayla
White, Alexander G
Causgrove, Chelsea
Stein, Brianne
Tomko, Jaime
Mattila, Joshua T
Gideon, Hannah
Lin, P Ling
Reimann, Keith A
Kirschner, Denise E
Flynn, JoAnne L
Journal of immunology (Baltimore, Md. : 1950) 2020 Feb 22;204(3): 644-659

Tuberculosis (TB), caused by , 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 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 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 infection.

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