title: Murine survival of infection with Francisella novicida and protection against secondary challenge is critically dependent on B lymphocytes.
abstract: Respiratory infection of mice with Francisella novicida has recently been used as a model for the highly virulent human pathogen Francisella tularensis. Similar to F. tularensis, even small doses of F. novicida administered by respiratory routes are lethal for inbred laboratory mice. This feature obviously limits study of infection-induced immunity. Parenteral sublethal infections of mice with F. novicida are feasible, but the resulting immune responses are incompletely characterized. Here we use parenteral intradermal (i.d.) and intraperitoneal (i.p.) F. novicida infections of C57BL/6J mice to determine the role of B cells in controlling primary and secondary F. novicida infections. Despite developing comparable levels of F. novicida-primed T cells, B cell knockout mice were much more susceptible to both primary i.d. infection and secondary i.p. challenge than wild type (normal) C57BL/6J mice. Transfer of F. novicida-immune sera to either wild type C57BL/6J mice or to B cell knockout mice did not appreciably impact survival of subsequent lethal F. novicida challenge. However, F. novicida-immune mice that were depleted of T cells after priming but just before challenge survived and cleared secondary i.p. F. novicida challenge. Collectively these results indicate that B cells, if not serum antibodies, play a major role in controlling F. novicida infections in mice.
authors.affiliation: Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, MD 20852, United States.
authors.forename: Alicia Y
authors.initials: AY
authors.lastname: Chou
authors.affiliation: Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, MD 20852, United States.
authors.forename: Nikki J
authors.initials: NJ
authors.lastname: Kennett
authors.affiliation: Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, MD 20852, United States.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Melillo
authors.affiliation: Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, MD 20852, United States. Electronic address: karen.elkins@fda.hhs.gov.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Elkins
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005603:Francisella / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000401:mortality* / Q000517:prevention & control*; D007271:Injections, Intradermal; D007274:Injections, Intraperitoneal; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012141:Respiratory Tract Infections / Q000401:mortality* / Q000517:prevention & control*; D016019:Survival Analysis
keywords: B lymphocytes; Francisella novicida; Francisella tularensis; Protective immunity; T lymphocytes