title: Increased susceptibility of IgA-deficient mice to pulmonary Francisella tularensis live vaccine strain infection.
abstract: Francisella tularensis, the causative agent of tularemia, is most deadly in the pneumonic form; therefore, mucosal immunity is an important first line of defense against this pathogen. We have now evaluated the lethality of primary F. tularensis live vaccine strain (LVS) pulmonary infection in mice that are defective in IgA (IgA(-/-) mice), the predominant mucosal Ig isotype. The results showed that IgA(-/-) mice were more susceptible than IgA(+/+) mice to intranasal F. tularensis LVS infection, despite developing higher levels of LVS-specific total, IgG, and IgM antibodies in the bronchoalveolar lavage specimens following infection. In addition, the absence of IgA resulted in a significant increase in bacterial loads and reduced survival. Interestingly, IgA(-/-) mice had lower pulmonary gamma interferon (IFN-γ) levels and decreased numbers of IFN-γ-secreting CD4(+) and CD8(+) T cells in the lung on day 9 postinfection compared to IgA(+/+) mice. Furthermore, IgA(-/-) mice displayed reduced interleukin 12 (IL-12) levels at early time points, and supplementing IgA(-/-) mice with IL-12 prior to LVS challenge induced IFN-γ production by NK cells and rescued them from mortality. Thus, IgA(-/-) mice are highly susceptible to primary pulmonary LVS infections not only because of IgA deficiency but also because of reduced IFN-γ responses.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furuya
authors.forename: Girish S
authors.initials: GS
authors.lastname: Kirimanjeswara
authors.forename: Sean
authors.initials: S
authors.lastname: Roberts
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D058491:Bacterial Load / Q000276:immunology; D018893:Bronchoalveolar Lavage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D005260:Female; D005604:Francisella tularensis / Q000276:immunology*; D017098:IgA Deficiency / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D014406:Tularemia / Q000276:immunology* / Q000382:microbiology; D014613:Vaccines, Attenuated / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014613:Vaccines, Attenuated; D018664:Interleukin-12; D007371:Interferon-gamma