Production of Anti-LPS IgM by B1a B Cells Depends on IL-1β and Is Protective against Lung Infection with LVS

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Francisella tularensis is a Gram-negative bacterium that infects macrophages and other cell types causing tularemia. F. tularensis is considered a potential bioterrorism agent and is a prime model intracellular bacterium to study the interaction of pathogens with the host immune system. The role of the proinflammatory cytokines IL-1β and IL-18 during lung infection with F. tularensis has not been characterized in detail. Here, using a mouse model of pneumonic tularemia, we show that both cytokines are protective, but through different mechanisms. Mice deficient in IL-18 quickly succumbed to the infection but administration of IFNγ rescued their survival. In contrast, mice lacking IL-1β appeared to control the infection in its early stages, but eventually succumbed and were not rescued by administration of IFNγ. Rather, IL-1β-deficient mice had significantly reduced serum level of IgM antibodies specific for F. tularensis LPS. These antibodies were generated in a IL-1β-, TLR2-, and ASC-dependent fashion, promoted bacteria agglutination and phagocytosis, and were protective in passive immunization experiments. B1a B cells produced the anti-F. tularensis IgM and were significantly decreased in the spleen and peritoneal cavity of infected IL-1β-deficient mice. Collectively, our results show that IL-1β and IL-18 activate non-redundant protective responses against tularemia and identify an essential role for IL-1β in the rapid generation of pathogen-specific IgM by B1a B cells.

Vyšlo v časopise: Production of Anti-LPS IgM by B1a B Cells Depends on IL-1β and Is Protective against Lung Infection with LVS. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004706
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004706

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