The Commensal Neisseria musculi Modulates Host Innate Immunity To Promote Oral Colonization

Daniel A. Powell, Mancheong Ma, Magdalene So, Jeffrey A. Frelinger

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Neisseria musculi, isolated from the oral cavity of wild-caught mice, does not colonize most inbred mouse strains. N. musculi does weakly (50%) colonize C57BL/6J (B6) mice but readily colonizes CAST/EiJ (CAST) mice. In this study, we examined whether differences in the CAST and B6 host response could elucidate mechanisms governing N. musculi colonization. In vivo stimulation of B6 or CAST splenocytes with wild type (WT) Neisseria or Escherichia coli LPS showed that CAST mice had a blunted inflammatory response, producing significantly lower levels of IL-6 than B6 mice. The use of specific genetic knockouts highlighted a need for an intact innate immune system to prevent colonization. B6–RAG-12/2 mice were colonized at a similar rate as WT B6 mice, whereas B6-MyD882/2 and TLR42/2 mice were readily colonized like CAST (100%) mice. Sequence analysis revealed a unique point mutation in TLR4 in CAST mice. However, crosses to TLR42/2 mice and analysis of recombinant inbred Collaborative Cross mice showed that TLR4 from CAST mice was not sufficient to allow Neisseria colonization. In vitro stimulation of B6 bone marrow–derived macrophages or splenocytes with WT Neisseria yielded low levels of IL-6 compared with LPS stimulation. Surprisingly, UV-inactivated Neisseria induced high levels of IL-6, suggesting suppression of IL-6 production is an active bacterial process. Consistent with a critical role for IL-6 in preventing colonization, mice deficient for the IL-6 receptor were efficiently colonized, indicating host IL-6 production plays a critical role in determining host colonization susceptibility.

Original languageEnglish (US)
Pages (from-to)305-313
Number of pages9
JournalImmunoHorizons
Volume2
Issue number9
DOIs
StatePublished - Oct 1 2018

ASJC Scopus subject areas

  • General Medicine
  • Immunology and Allergy
  • Immunology

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