TLR2, but not TLR4, plays a predominant role in the immune responses to cholera vaccines

Jae Seung Yang, Hye Jin Kim, Seok Seong Kang, Kyoung Whun Kim, Dong Wook Kim, Cheol Heui Yun, Soon Jung Park, Ho Seong Seo, B. Brett Finlay, Seung Hyun Han

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Vibrio cholerae can cause severe diarrhea and dehydration leading to high mortality and morbidity. Current cholera vaccines are formulated with KVC. Although the innate immune responses following vaccination deeply influence the induction of adaptive immunity, the initial recognition of cholera vaccines by the host innate immune system is not well characterized. In this study, the ability of KVC to induce innate immune responses was investigated. Unlike typical Gram-negative bacteria stimulating TLR2 and TLR4, KVC activated TLR2 but hardly TLR4. However, purified V. cholerae LPS prefer- entially stimulated TLR4, although not as potently as LPS of other Gram-negative bacteria, implying that LPS is not a major immunostimulatory component of KVC. Instead, MPFs were similar to KVC in the capacity to activate TLR2, transcription factors, and cytokine expression. Furthermore, OmpU is an abundant membrane protein of V. cholerae and could interact with TLR2 for inducing cytokine expression. Notably, cholera vaccine-induced immune responses are impaired in TLR2-/- mice. Conclusively, TLR2 is essential for the immune responses to cholera vaccination, and OmpU is the major immunostimulatory component of cholera vaccines.

Original languageEnglish
Pages (from-to)661-669
Number of pages9
JournalJournal of Leukocyte Biology
Volume98
Issue number4
DOIs
StatePublished - Oct 2015

Keywords

  • Innate immunity
  • OmpU
  • Vibrio cholera

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