Downmodulation of Vaccine-Induced Immunity and Protection against the Intracellular Bacterium Francisella tularensis by the Inhibitory Receptor FcγRIIB. (19th April 2015)

• Record Type: Journal Article
• Authors: Franz, Brian J.; Li, Ying; Bitsaktsis, Constantine; Iglesias, Bibiana V.; Pham, Giang; Sunagar, Raju; Kumar, Sudeep; Gosselin, Edmund J.
• Other Names: Bottasso Oscar Academic Editor.
• Is Part Of: Journal of immunology research. Volume 2015(2015)
• Publication Date: 2015-04-19
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2015/840842
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : Fc gamma receptor IIB (Fc γ RIIB) is the only Fc gamma receptor (Fc γ 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 γ RIIB on immune protection against Francisella tularensis ( Ft ), a Category A biothreat agent. We utilized inactivated Ft (i Ft ) as an immunogen. Naïve and i Ft -immunized Fc γ RIIB knockout (KO) or wildtype (WT) mice were challenged with Ft -live vaccine strain (LVS). While no significant difference in survival between naïve Fc γ RIIB KO versus WT mice was observed, i Ft -immunized Fc γ RIIB KO mice were significantly better protected than i Ft -immunized WT mice. Ft -specific IgA in serum and bronchial alveolar lavage, as well as IFN- γ, IL-10, and TNF- α production by splenocytes harvested from i Ft -immunized Fc γ RIIB KO, were also significantly elevated. In addition, i Ft -immunized Fc γ 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 γ 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.