Production of anti-LPS IgM by B1a B cells depends on IL-1β and is protective against lung infection with Francisella tularensis LVS

PLoS Pathogens
Laura Del BarrioFabio Re

Abstract

The role of IL-1β and IL-18 during lung infection with the gram-negative bacterium Francisella tularensis LVS 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. Il-18-/- mice quickly succumb to the infection and showed higher bacterial burden in organs and lower level of IFNγ in BALF and serum compared to wild type C57BL/6J mice. Administration of IFNγ rescued the survival of Il-18-/- mice, suggesting that their decreased resistance to tularemia is due to inability to produce IFNγ. In contrast, mice lacking IL-1 receptor or IL-1β, but not IL-1α, appeared to control the infection in its early stages, but eventually succumbed. IFNγ administration had no effect on Il-1r1-/- mice survival. Rather, Il-1r1-/- mice were found to have significantly reduced titer of Ft LPS-specific IgM. The anti-Ft LPS IgM was generated in a IL-1β-, TLR2-, and ASC-dependent fashion, promoted bacteria agglutination and phagocytosis, and was protective in passive immunization experiments. B1a B cells produced the anti-Ft LPS IgM and these cells were significantly decreased in the spleen and peritoneal cavity of infected Il-1b-/- mice, compare...Continue Reading

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Citations

Nov 9, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qifan ZhuThirumala-Devi Kanneganti
Nov 14, 2019·Cellular and Molecular Life Sciences : CMLS·Qiyao ChaiCui Hua Liu
Jun 2, 2020·PLoS Computational Biology·Jonathan CarruthersCarmen Molina-París
Jun 6, 2017·Nature Communications·Sivakumar PeriasamyJonathan A Harton
Nov 17, 2020·Frontiers in Immunology·Katelyn JonesSabelo Hadebe
Sep 23, 2021·Expert Review of Vaccines·Henderson ZhuAndrew J Pollard

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Methods Mentioned

BETA
bronchoalveolar lavage
ELISA
flow cytometry
PMA
FACS
FCS

Software Mentioned

GraphPad Prism
FlowJo

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