FcγRIIB limits protection against F. tularensis LVS challenge induced by inactivated F. tularensis immunogen (P4294)

Abstract

Abstract We have previously shown that intranasal immunization with inactivated Francisella tularensis LVS targeted to FcR induces partial protection against a mucosal challenge with F. tularensis SchuS4 and that this protection is Ab and IFN-γ dependent. FcγRIIB, the only inhibitory FcγR, has been reported to regulate IgG production, which plays a major role in protection against F. tularensis LVS and SchuS4 challenge. Thus, we sought to determine the impact of FcγRIIB on immune protection against F. tularensis infection. We utilized inactivated F. tularensis as an immunogen. Naïve or inactivated F. tularensis-immunized FcγRIIB knockout versus wildtype C57BL/6 mice were challenged with varying doses of F. tularensis LVS. While we observed no difference in survival between naïve knockout versus wildtype mice, knockout mice immunized with inactivated F. tularensis showed significantly increased survival as compared to similarly immunized wildtype mice. Also, both F. tularensis-specific IgG and IgA production were elevated in serum and bronchoalveolar lavage fluid from inactivated F. tularensis-immunized knockout versus wildtype mice, as was IFN-γ production. In summary, our studies show that FcγRIIB limits the level of protection against F. tularensis challenge generated by inactivated F. tularensis immunization, by limiting the production of F. tularensis-specific IgG, IgA, and IFN-γ, which have been shown to be important for protection against F. tularensis infection.