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

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,compared to c57bl/6j 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. © 2015 del barrio et al.