IL-4-responsive B cells are detrimental during chronic tuberculosis infection in mice. Parihar, S. P, Ozturk, M., Höft, M. A, Chia, J. E, Guler, R., Keeton, R., van Rensburg, I. C, Loxton, A. G, & Brombacher, F. Frontiers in Immunology, 12:611673, Frontiers, jun, 2021.
IL-4-responsive B cells are detrimental during chronic tuberculosis infection in mice [link]Paper  doi  abstract   bibtex   
In tuberculosis, T cell-mediated immunity is extensively studied whilst B cells received limited attention in humans and mice. Of interest, Mycobacterium tuberculosis (Mtb) does increase IL-4 Receptor-alpha (IL4Ra) expression in murine B cells. To better understand the role of IL4Ra expression in B cells, we compared wild type mice with B cell-specific IL4Ra-deficient mice (mb1creIL-4R$α$-/lox mice) to understand the role of IL-4R$α$ signaling in B cells. Chronic Mtb aerosol infection in mb1creIL-4R$α$-/lox mice reduced lung and spleen bacterial burdens, compared to littermate (IL-4R$α$-/lox) control animals. Consequently, lung pathology, inflammation, and inducible nitric oxide synthase (iNOS) expression were reduced in the lungs of mb1creIL-4R$α$-/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 IL4Ra-deficient mice reversed the protective phenotype. Moreover, using constitutively mCherry expressing Mtb we showed decreased association with B cells from mb1creIL-4R$α$-/lox mice ex vivo. In addition, supernatants from Mtb-exposed B cells of mb1creIL-4R$α$-/lox mice also increased the ability of macrophages to produce nitric oxide, IL-1$β$, and IL-6. 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 stat1 levels in the lungs.
@article{Parihar2021,
abstract = {In tuberculosis, T cell-mediated immunity is extensively studied whilst B cells received limited attention in humans and mice. Of interest, Mycobacterium tuberculosis (Mtb) does increase IL-4 Receptor-alpha (IL4Ra) expression in murine B cells. To better understand the role of IL4Ra expression in B cells, we compared wild type mice with B cell-specific IL4Ra-deficient mice (mb1creIL-4R$\alpha$-/lox mice) to understand the role of IL-4R$\alpha$ signaling in B cells. Chronic Mtb aerosol infection in mb1creIL-4R$\alpha$-/lox mice reduced lung and spleen bacterial burdens, compared to littermate (IL-4R$\alpha$-/lox) control animals. Consequently, lung pathology, inflammation, and inducible nitric oxide synthase (iNOS) expression were reduced in the lungs of mb1creIL-4R$\alpha$-/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 IL4Ra-deficient mice reversed the protective phenotype. Moreover, using constitutively mCherry expressing Mtb we showed decreased association with B cells from mb1creIL-4R$\alpha$-/lox mice ex vivo. In addition, supernatants from Mtb-exposed B cells of mb1creIL-4R$\alpha$-/lox mice also increased the ability of macrophages to produce nitric oxide, IL-1$\beta$, and IL-6. 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 stat1 levels in the lungs.},
author = {Parihar, Suraj P and Ozturk, Mumin and H{\"{o}}ft, Maxine A and Chia, Julius E and Guler, Reto and Keeton, Roanne and van Rensburg, Ilana C and Loxton, Andre G and Brombacher, Frank},
doi = {10.3389/FIMMU.2021.611673},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Parihar et al. - 2021 - IL-4-responsive B cells are detrimental during chronic tuberculosis infection in mice.pdf:pdf},
issn = {1664-3224},
journal = {Frontiers in Immunology},
keywords = {B cells,IL-4RA,Mice (balb/c),OA,OA{\_}PMC,TB,fund{\_}ack,human,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,original},
month = {jun},
pages = {611673},
pmid = {34220793},
publisher = {Frontiers},
title = {{IL-4-responsive B cells are detrimental during chronic tuberculosis infection in mice}},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2021.611673/full},
volume = {12},
year = {2021}
}

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