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

Autor: Mi-Na Kweon, Jae-Hee Ahn, Pyeung-Hyeun Kim, Hyungjun Yang, Sung-il Yoon, Sun-Young Chang, Hyun-Jeong Ko, Jaewon Cho, Geun-Shik Lee, Bruce A. Vallance, Bo-Eun Kwon, Young-In Kim, Seung Goo Kang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Lipopolysaccharides
Salmonella typhimurium
Salmonella
Live attenuated vaccines
Salmonella Vaccines
medicine.medical_treatment
Administration
Oral
lcsh:Medicine
Salmonella infection
Inflammation
Biology
medicine.disease_cause
Vaccines
Attenuated
Article
Microbiology
03 medical and health sciences
Interferon-gamma
0302 clinical medicine
Immune system
Immunity
medicine
Animals
lcsh:Science
Adaptor Proteins
Signal Transducing
Multidisciplinary
Virulence
lcsh:R
Cell Differentiation
Salmonella vaccine
Antimicrobial responses
Th1 Cells
medicine.disease
Germinal Center
Mice
Inbred C57BL
030104 developmental biology
Cytokine
Immunoglobulin class switching
Immunoglobulin G
Chronic Disease
Salmonella Infections
Immunization
lcsh:Q
medicine.symptom
Bacterial infection
030217 neurology & neurosurgery
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-019-44019-3
Popis: Inhibitor of kappa B (IκB)-ζ transcription is rapidly induced by stimulation with TLR ligands and IL-1. Despite high IκBζ expression in inflammation sites, the association of IκBζ 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 IκBζ-deficient mice against a lethal Salmonella challenge. IκBζ-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, IκBζ-deficient mice exhibited enhanced splenic germinal centre reactions followed by increased total IgG production, despite IκBζ-deficient B cells having an intrinsic antibody class switching defect. IκBζ-deficient CD4+ T cells poorly differentiated into Th1 cells. IFN-γ production by CD4+ T cells from IκBζ-deficient mice immunised with RASV significantly decreased after restimulation with heat-killed RASV in vitro, suggesting that IκBζ-deficient mice failed to mount protective immune responses against Salmonella infection because of insufficient Th1 and IgG production. Therefore, IκBζ is crucial in protecting against Salmonella infection by inducing Th1 differentiation followed by IgG production.
Databáze: OpenAIRE
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