B cells promote granulomatous inflammation during chronic Mycobacterium tuberculosis infection in mice.
B cells promote granulomatous inflammation during chronic Mycobacterium tuberculosis infection in mice.
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B细胞在小鼠的慢性分枝杆菌感染期间促进肉芽肿性炎症。
DOI：
10.1371/journal.ppat.1011187
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发表时间：
2023-03
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
目前的研究表明，在慢性结核病中，与野生型（WT） C57BL/6小鼠相比，B细胞缺陷μMT菌株在肺部显示出较低水平的炎症，这与CD4+ T细胞增殖减少、Th1反应减弱和白细胞介素(IL)-10水平升高有关。后一结果提出了B细胞可能限制慢性结核患者肺中IL-10表达的可能性。这些观察结果在使用抗cd20抗体去除B细胞的WT小鼠中得到了重述。IL-10受体（IL-10R）阻断逆转了B细胞枯竭小鼠炎症减少和CD4+ T细胞反应减弱的表型。总之，这些结果表明，在慢性结核小鼠中，B细胞凭借其限制肺中抗炎和免疫抑制IL-10表达的能力，促进了强大的保护性Th1反应的发展，从而优化了抗结核免疫。然而，这种强烈的Th1免疫和受限的IL-10表达可能会使炎症发展到对宿主有害的水平。事实上，在慢性感染的B细胞缺陷小鼠中观察到的肺部炎症减少，表现出肺部IL-10水平的增加，与WT动物的生存优势有关。总的来说，结果表明，在慢性小鼠结核病中，B细胞在调节保护性Th1免疫和抗炎IL-10反应中发挥作用，从而导致肺部炎症的增强，这可能对宿主有害。有趣的是，在人类结核肺中，明显的B细胞聚集物存在于组织损伤病灶附近，表现为坏死和空化，这表明在人类结核病中，B细胞可能促进了已知的促进传播的加重病理的发展。由于传播是结核病控制的主要障碍，因此有必要研究B细胞是否可以影响结核病患者严重肺部病理反应的发展。结核分枝杆菌仍然是世界范围内的一个主要公共卫生威胁。在结核感染期间，保护反应和潜在的组织损伤炎症的平衡影响疾病的结局。慢性结核可伴有肺损伤性炎症，导致坏死和空洞形成，这些病理过程有利于结核分枝杆菌的传播。限制传播是控制结核的重要措施。我们启动了实验来表征B细胞在慢性结核病中调节肺部炎症的作用，慢性结核病是最可能发生组织损伤炎症的感染阶段。结果提示，B细胞可通过提高产生保护性干扰素(IFN)-γ的CD4+ T细胞水平，同时抑制免疫抑制、抗炎的IL-10的表达，从而推动慢性TB肺部炎症的发展。因此，在慢性感染中，B细胞可能有助于最佳的结核病控制，但矛盾的是促进肺部病理。了解B细胞如何调节结核病中的肺部炎症可能有助于设计减少传播的策略，从而实现更好的结核病控制。
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. Mycobacterium tuberculosis remains a major public health threat worldwide. Balancing of the protective response and potentially tissue-damaging inflammation during tuberculous infection influences disease outcome. Chronic TB can be associated with lung-damaging inflammation, resulting in necrotization and cavity formation, pathological processes that are conducive to the transmission of M. tuberculosis. Restricting transmission is an important measure for TB control. We initiated experiments to characterize the role of B cells in modulating lung inflammation in chronic TB, the phase of infection during which tissue-damaging inflammation is most likely to occur. The results suggest that B cells can drive the development of lung inflammation in chronic TB by enhancing the levels of protective interferon (IFN)-γ-producing CD4+ T cells while restricting the expression of the immunosuppressive, anti-inflammatory IL-10. Thus, in chronic infection, B cells may contribute to optimal TB control but paradoxically promote lung pathology. Understanding how B cells regulate lung inflammation in TB may help the design of strategies that can reduce transmission, thereby achieving better TB control.
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影响因子：
30.5
作者：
Bermejo, Daniela A.;Jackson, Shaun W.;Gorosito-Serran, Melisa;Acosta-Rodriguez, Eva V.;Amezcua-Vesely, Maria C.;Sather, Blythe D.;Singh, Akhilesh K.;Khim, Socheath;Mucci, Juan;Liggitt, Denny;Campetella, Oscar;Oukka, Mohamed;Gruppi, Adriana;Rawlings, David J.
通讯作者：
Rawlings, David J.
DOI：
10.4049/jimmunol.181.8.5545
发表时间：
2008-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Beamer GL;Flaherty DK;Assogba BD;Stromberg P;Gonzalez-Juarrero M;de Waal Malefyt R;Vesosky B;Turner J
通讯作者：
Turner J
DOI：
10.4049/jimmunol.1202722
发表时间：
2013-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cyktor JC;Carruthers B;Kominsky RA;Beamer GL;Stromberg P;Turner J
通讯作者：
Turner J
DOI：
10.1038/s41577-019-0131-x
发表时间：
2019-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Altan-Bonnet G;Mukherjee R
通讯作者：
Mukherjee R
DOI：
10.1073/pnas.1611987113
发表时间：
2016-09-20
影响因子：
11.1
作者：
Foreman, Taylor W.;Mehra, Smriti;Kaushal, Deepak
通讯作者：
Kaushal, Deepak