AUTHOR=Parihar Suraj P. , Ozturk Mumin , Höft Maxine A. , Chia Julius E. , Guler Reto , Keeton Roanne , van Rensburg Ilana C. , Loxton Andre G. , Brombacher Frank TITLE=IL-4-Responsive B Cells Are Detrimental During Chronic Tuberculosis Infection in Mice JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.611673 DOI=10.3389/fimmu.2021.611673 ISSN=1664-3224 ABSTRACT=

In tuberculosis, T cell-mediated immunity is extensively studied whilst B cells received limited attention in human and mice. Of interest, Mycobacterium tuberculosis (Mtb) does increase IL-4 Receptor-alpha (IL4Rα) expression in murine B cells. To better understand the role of IL4Rα signalling in B cells, we compared wild type mice with B cell-specific IL4Rα deficient mice (mb1^creIL-4Rα^-/lox mice). Chronic Mtb aerosol infection in mb1^creIL-4Rα^-/lox mice reduced lung and spleen bacterial burdens, compared to littermate (IL-4Rα^-/lox) control animals. Consequently, lung pathology, inflammation and inducible nitric oxide synthase (iNOS) expression were reduced in the lungs of mb1^creIL-4Rα^-/lox mice, which was also accompanied by increased lung IgA and decreased IgG1 levels. Furthermore, intratracheal adoptive transfer of wild-type B cells into B cell-specific IL4Rα deficient mice reversed the protective phenotype. Moreover, constitutively mCherry expressing Mtb showed decreased association with B cells from mb1^creIL-4Rα^-/lox mice ex vivo. In addition, supernatants from Mtb-exposed B cells of mb1^creIL-4Rα^-/lox mice also increased the ability of macrophages to produce nitric oxide, IL-1β, IL-6 and TNF. Together, this demonstrates that IL-4-responsive B cells are detrimental during the chronic phase of tuberculosis in mice with perturbed antibody profiles, inflammatory cytokines and tnf and stat1 levels in the lungs.