IκBζ facilitates protective immunity against Salmonella infection via Th1 differentiation and IgG production

초록

Inhibitor of kappa B (I kappa,B)-zeta transcription is rapidly induced by stimulation with TLR ligands and IL-1. Despite high I kappa B zeta expression in inflammation sites, the association of I kappa B zeta with host defence via systemic immune responses against bacterial infection remains unclear. Oral immunisation with a recombinant attenuated Salmonella vaccine (RASV) strain did not protect I kappa B zeta-deficient mice against a lethal Salmonella challenge. I kappa B zeta-deficient mice failed to produce Salmonella LPS-specific IgG, especially IgG2a, although inflammatory cytokine production and immune cell infiltration into the liver increased after oral RASV administration. Moreover, I kappa B zeta-deficient mice exhibited enhanced splenic germinal centre reactions followed by increased total IgG production, despite I kappa B zeta-deficient B cells having an intrinsic antibody class switching defect. I kappa B zeta-deficient CD4(+) T cells poorly differentiated into Th1 cells. IFN-gamma production by CD4(+) T cells from I kappa B zeta -deficient mice immunised with RASV significantly decreased after restimulation with heat-killed RASV in vitro, suggesting that I kappa B zeta-deficient mice failed to mount protective immune responses against Salmonella infection because of insufficient Th1 and IgG production. Therefore, I kappa B zeta is crucial in protecting against Salmonella infection by inducing Th1 differentiation followed by IgG production.

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