Innate immunity mediated by MyD88 signal is not essential for induction of lipopolysaccharide-specific B cell responses but is indispensable for protection against Salmonella enterica serovar Typhimurium infection

Hyun Jeong Ko, Jin Young Yang, Doo Hee Shim, Hyungjun Yang, Sung Moo Park, Roy Curtiss, Mi Na Kweon

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Abstract

Salmonella organisms are Gram negative and facultative anaerobic bacteria that cause typhoid fever in humans. In this study, we evaluated LPS-specific adaptive immunity in innate immune-deficient mice after oral administration of attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) strains. Of interest, identical levels of LPS-specific IgG and IgA Abs were elicited in the systemic (i.e., serum and spleen) and mucosal (i.e., fecal extract and small intestine) compartments of wild-type, TLR4-/-, and MyD88 -/- mice following oral vaccination with recombinant attenuated S. Typhimurium (RASV). Depletion of CD4+ T cells during RASV vaccination completely abrogated the generation of LPS-specific Abs in MyD88-/- mice. In addition, mRNA expression levels of a B cell-activating factor of the TNF family were significantly increased in the spleens of MyD88-/- mice after oral administration, implying that T cell-independent B cell switching might be also enhanced in the MyD88 signal-deficient condition. Of most interest, orally vaccinated MyD88-/- mice that possessed high levels of LPS-specific IgG and IgA, which had a neutralizing effect against Salmonella, died earlier than nonvaccinated wild-type mice following lethal oral challenge with virulent Salmonella species. These results suggest that innate immunity mediated by MyD88 signal is dispensable for induction of LPS-specific Ab responses following oral administration of attenuated Salmonella strains but indispensable for efficient protection.

Original languageEnglish (US)
Pages (from-to)2305-2312
Number of pages8
JournalJournal of Immunology
Volume182
Issue number4
DOIs
StatePublished - Feb 15 2009

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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