科研之友
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摘要
We have previously demonstrated that immunization with the inactivated Francisella tularensis, a Category A intracellular mucosal pathogen, combined with IgG2a anti-E tularensis monoclonal antibody (Ab), enhances protection against subsequent E tularensis challenge. To understand the mechanism(s) involved, we examined the binding, internalization, presentation, and in vivo trafficking of inactivated E tularensis in the presence and absence of opsonizing monoclonal Ab. We found that when inactivated E tularensis is combined with anti-E tularensis monoclonal Ab, presentation to F. tularensis-specific T cells is enhanced. This enhancement is Fc receptor (FcR)-dependent, and requires a physical linkage between the monoclonal Ab and the inactivated E tularensis immunogen. This enhanced presentation is due, in part, to enhanced binding and internalization of inactivated E tularensis by antigen(Ag)-presenting cells, and involves interactions with multiple FcR types. Furthermore, targeting inactivated E tularensis to FcRs enhances dendritic cell maturation and extends the time period over which Ag-presenting cells stimulate T cells. In vivo trafficking studies reveal enhanced transport of inactivated E tularensis immunogen to the nasal-associated lymphoid tissue in the presence of monoclonal Ab, which is FcRn-dependent. In summary, these are the first comprehensive studies using a single-vaccine protection model/immunogen to establish the array of mechanisms involved in enhanced immunity/protection mediated by an FcR-targeted mucosal immunogen. These results demonstrate that multiple cellular/immune mechanisms contribute to FcR-enhanced immunity. Immunology and Cell Biology (2013) 91, 139-148; doi:10.1038/icb.2012.66; published online 18 December 2012
- 出版日期2013-2
