Enhanced protection to <i>Mycobacterium tuberculosis</i> infection in IL‐10‐deficient mice is accompanied by early and enhanced Th1 responses in the lung

TLDR

IL‑10 modulates the immune response to balance pathogen clearance with immunopathology. IL‑10‑deficient mice infected with Mtb exhibit accelerated IFN‑γ‑driven Th1 responses, increased CD4⁺ T‑cell infiltration, and heightened chemokine/cytokine production, leading to lower lung bacterial loads and, when IL‑17 is neutralized, reduced splenic dissemination.

Abstract

IL-10 regulates the balance of an immune response between pathogen clearance and immunopathology. We show here that Mycobacterium tuberculosis (Mtb) infection in the absence of IL-10 (IL-10(-/-) mice) results in reduced bacterial loads in the lung. This reduction was preceded by an accelerated and enhanced IFN-γ response in the lung, an increased influx of CD4(+) T cells into the lung, and enhanced production of chemokines and cytokines, including CXCL10 and IL-17, in both the lung and the serum. Neutralization of IL-17 affected neither the enhanced production of CXCL10 nor the accumulation of IFN-γ-producing T cells in the lungs, but led to reduced numbers of granulocytes in the lung and reduced bacterial loads in the spleens of Mtb-infected mice. This suggests that IL-17 may contribute to dissemination of Mtb.