IL-4-Responsive B Cells Are Detrimental During Chronic Tuberculosis Infection in Mice.
Front Immunol
; 12: 611673, 2021.
Article
in En
| MEDLINE
| ID: mdl-34220793
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 (mb1creIL-4Rα-/lox mice). Chronic Mtb aerosol infection in mb1creIL-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 mb1creIL-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 mb1creIL-4Rα-/lox mice ex vivo. In addition, supernatants from Mtb-exposed B cells of mb1creIL-4Rα-/lox mice also increased the ability of macrophages to produce nitric oxide, IL-1ß, 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tuberculosis
/
Immunoglobulin A
/
B-Lymphocytes
/
Interleukin-4
/
Lung
/
Macrophages
/
Mycobacterium tuberculosis
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Front Immunol
Year:
2021
Type:
Article
Affiliation country:
South Africa