First Author | Ahn JH | Year | 2019 |
Journal | Sci Rep | Volume | 9 |
Issue | 1 | Pages | 8397 |
PubMed ID | 31182790 | Mgi Jnum | J:279757 |
Mgi Id | MGI:6357443 | Doi | 10.1038/s41598-019-44019-3 |
Citation | Ahn JH, et al. (2019) IkappaBzeta facilitates protective immunity against Salmonella infection via Th1 differentiation and IgG production. Sci Rep 9(1):8397 |
abstractText | Inhibitor of kappa B (IkappaB)-zeta transcription is rapidly induced by stimulation with TLR ligands and IL-1. Despite high IkappaBzeta expression in inflammation sites, the association of IkappaBzeta 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 IkappaBzeta-deficient mice against a lethal Salmonella challenge. IkappaBzeta-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, IkappaBzeta-deficient mice exhibited enhanced splenic germinal centre reactions followed by increased total IgG production, despite IkappaBzeta-deficient B cells having an intrinsic antibody class switching defect. IkappaBzeta-deficient CD4(+) T cells poorly differentiated into Th1 cells. IFN-gamma production by CD4(+) T cells from IkappaBzeta-deficient mice immunised with RASV significantly decreased after restimulation with heat-killed RASV in vitro, suggesting that IkappaBzeta-deficient mice failed to mount protective immune responses against Salmonella infection because of insufficient Th1 and IgG production. Therefore, IkappaBzeta is crucial in protecting against Salmonella infection by inducing Th1 differentiation followed by IgG production. |