Downmodulation of Vaccine-Induced Immunity and Protection against the Intracellular Bacterium Francisella tularensis by the Inhibitory Receptor Fc gamma RIIB

作者：Franz Brian J; Li Ying; Bitsaktsis Constantine; Iglesias Bibiana V; Pham Giang; Sunagar Raju; Kumar Sudeep; Gosselin Edmund J^*

来源：Journal of Immunology Research, 2015, 2015: 840842.

DOI：10.1155/2015/840842

Fc gamma receptor IIB (Fc gamma RIIB) is the only Fc gamma receptor (Fc gamma R) which negatively regulates the immune response, when engaged by antigen-(Ag-) antibody (Ab) complexes. Thus, the generation of Ag-specific IgG in response to infection or immunization has the potential to downmodulate immune protection against infection. Therefore, we sought to determine the impact of Fc gamma RIIB on immune protection against Francisella tularensis (Ft), a Category A biothreat agent. We utilized inactivated Ft (iFt) as an immunogen. Naive and iFt-immunized Fc gamma RIIB knockout (KO) or wildtype (WT) mice were challenged with Ft-live vaccine strain (LVS). While no significant difference in survival between naive Fc gamma RIIB KO versus WT mice was observed, iFt-immunized Fc gamma RIIB KO mice were significantly better protected than iFt-immunized WT mice. Ft-specific IgA in serum and bronchial alveolar lavage, as well as IFN-gamma, IL-10, and TNF-alpha production by splenocytes harvested from iFt-immunized Fc gamma RIIB KO, were also significantly elevated. In addition, iFt-immunized Fc gamma RIIB KO mice exhibited a reduction in proinflammatory cytokine levels in vivo at 5 days after challenge, which correlates with increased survival following Ft-LVS challenge in published studies. Thus, these studies demonstrate for the first time the ability of Fc gamma RIIB to regulate vaccine-induced IgA production and downmodulate immunity and protection. The immune mechanisms behind the above observations and their potential impact on vaccine development are discussed.

• 出版日期2015