title: Production of anti-LPS IgM by B1a B cells depends on IL-1β and is protective against lung infection with Francisella tularensis LVS.
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, 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.
authors.affiliation: Department of Microbiology & Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: del Barrio
authors.affiliation: Department of Microbiology & Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, United States of America.
authors.forename: Manoranjan
authors.initials: M
authors.lastname: Sahoo
authors.affiliation: Department of Microbiology & Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, United States of America.
authors.forename: Louis
authors.initials: L
authors.lastname: Lantier
authors.affiliation: Department of Microbiology & Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, United States of America.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Reynolds
authors.affiliation: Department of Microbiology & Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, United States of America.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Ceballos-Olvera
authors.affiliation: Department of Microbiology & Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, United States of America.
authors.forename: Fabio
authors.initials: F
authors.lastname: Re
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012141:Respiratory Tract Infections / Q000276:immunology; D014406:Tularemia / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007075:Immunoglobulin M; D053583:Interleukin-1beta; D008070:Lipopolysaccharides