Inflammation Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and.
J Immunol. 2014 Jun 1;192(11):5265-72. doi: 10.4049/jimmunol.1400087. Epub 2014 Apr 18.
We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice, a property known as heterologous immunity. Lactobacillus priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. Because B cells have been shown to promote heterologous immunity against respiratory virus pathogens under similar conditions, in this study we explore the role of B cells in Lactobacillus-mediated protection against acute pneumovirus infection. We found that Lactobacillus-primed mice feature elevated levels of airway Igs IgG, IgA, and IgM and lung tissues with dense, B cell (B220(+))-enriched peribronchial and perivascular infiltrates with germinal centers consistent with descriptions of BALT. No B cells were detected in lung tissue of Lactobacillus-primed B cell deficient μMT mice or Jh mice, and Lactobacillus-primed μMT mice had no characteristic infiltrates or airway Igs. Nonetheless, we observed diminished virus recovery and profound suppression of virus-induced proinflammatory cytokines CCL2, IFN-γ, and CXCL10 in both wild-type and Lactobacillus-primed μMT mice. Furthermore, Lactobacillus plantarum-primed, B cell-deficient μMT and Jh mice were fully protected from an otherwise lethal pneumonia virus of mice infection, as were their respective wild-types. We conclude that B cells are dispensable for Lactobacillus-mediated heterologous immunity and were not crucial for promoting survival in response to an otherwise lethal pneumovirus infection.
我们之前已经表明,用活的乳杆菌属物种对呼吸道黏膜进行预刺激可促进对小鼠肺炎病毒的致命感染产生强大而持久的存活,这种特性被称为异源免疫。乳杆菌属的预刺激导致病毒回收量适度减少和病毒诱导的促炎细胞因子产生显著减少;这些发现的确切机制仍有待阐明。因为已经表明 B 细胞在类似条件下可以促进针对呼吸道病毒病原体的异源免疫,所以在这项研究中,我们探索了 B 细胞在乳杆菌介导的对急性副黏液病毒感染的保护作用中的作用。我们发现,乳杆菌预刺激的小鼠具有高水平的气道 IgG、IgA 和 IgM,并且肺组织中存在密集的 B 细胞(B220(+))丰富的支气管周围和血管周围浸润,其中有生发中心,与描述的支气管相关淋巴组织(BALT)一致。在乳杆菌预刺激的 B 细胞缺陷 μMT 小鼠或 Jh 小鼠的肺组织中未检测到 B 细胞,并且乳杆菌预刺激的 μMT 小鼠没有特征性浸润或气道 Ig。尽管如此,我们观察到在野生型和乳杆菌预刺激的 μMT 小鼠中,病毒回收量减少,并且病毒诱导的促炎细胞因子 CCL2、IFN-γ 和 CXCL10 受到深刻抑制。此外,乳杆菌植物乳杆菌预刺激、B 细胞缺陷 μMT 和 Jh 小鼠完全免受致命性的小鼠肺炎病毒感染,其各自的野生型也是如此。我们得出结论,B 细胞对于乳杆菌介导的异源免疫是可有可无的,并且对于促进对致命性副黏液病毒感染的存活不是至关重要的。