B cells promote granulomatous inflammation during chronic Mycobacterium tuberculosis infection in mice.

Abstract

The current study reveals that in chronic TB, the B cell-deficient μMT strain, relative to wild-type (WT) C57BL/6 mice, displays in the lungs lower levels of inflammation that are associated with decreased CD4+ T cell proliferation, diminished Th1 response, and enhanced levels of interleukin (IL)-10. The latter result raises the possibility that B cells may restrict lung expression of IL-10 in chronic TB. These observations are recapitulated in WT mice depleted for B cells using anti-CD20 antibodies. IL-10 receptor (IL-10R) blockade reverses the phenotypes of decreased inflammation and attenuated CD4+ T cell responses in B cell-depleted mice. Together, these results suggest that in chronic murine TB, B cells, by virtue of their capacity to restrict expression of the anti-inflammatory and immunosuppressive IL-10 in the lungs, promote the development of a robust protective Th1 response, thereby optimizing anti-TB immunity. This vigorous Th1 immunity and restricted IL-10 expression may, however, allow the development of inflammation to a level that can be detrimental to the host. Indeed, decreased lung inflammation observed in chronically infected B cell-deficient mice, which exhibit augmented lung IL-10 levels, is associated with a survival advantage relative to WT animals. Collectively, the results reveal that in chronic murine TB, B cells play a role in modulating the protective Th1 immunity and the anti-inflammatory IL-10 response, which results in augmentation of lung inflammation that can be host-detrimental. Intriguingly, in tuberculous human lungs, conspicuous B cell aggregates are present in close proximity to tissue-damaging lesions manifesting necrosis and cavitation, suggesting the possibility that in human TB, B cells may contribute to the development of exacerbated pathology that is known to promote transmission. Since transmission is a major hindrance to TB control, investigating into whether B cells can shape the development of severe pulmonic pathological responses in tuberculous individuals is warranted.

• Authors: Yong Chen, Sushma Bharrhan, Jiayong Xu, Tarina Sharma, Yanhua Wang, Padmini Salgame, Jinghang Zhang, Kievershen Nargan, Adrie J C Steyn, Paul J Maglione, John Chan
• Journal: PLoS pathogens (PLoS Pathog) Vol. 19 Issue 3 Pg. e1011187 (03 2023) ISSN: 1553-7374 [Electronic] United States
• PMID: 36888692 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Chemical References

• Interleukin-10

Topics

• Mice
• Humans
• Animals
• Interleukin-10 (metabolism)
• Mycobacterium tuberculosis
• Mice, Inbred C57BL
• Tuberculosis
• Tuberculosis, Pulmonary
• Inflammation
• Th1 Cells