MyD88 expression by CNS-resident cells is pivotal for eliciting protective immunity in brain abscesses

Sarita Garg, Jessica R. Nichols, Nilufer Esen, Shuliang Liu, Nirmal K. Phulwani, Mohsin Md Syed, William H. Wood, Yongqing Zhang, Kevin G. Becker, Amy Aldrich, Tammy Kielian

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

MyD88 KO (knockout) mice are exquisitely sensitive to CNS (central nervous system) infection with Staphylococcus aureus, a common aetiological agent of brain abscess, exhibiting global defects in innate immunity and exacerbated tissue damage. However, since brain abscesses are typified by the involvement of both activated CNS-resident and infiltrating immune cells, in our previous studies it has been impossible to determine the relative contribution of MyD88-dependent signalling in the CNS compared with the peripheral immune cell compartments. In the present study we addressed this by examining the course of S. aureus infection in MyD88 bone marrow chimaera mice. Interestingly, chimaeras where MyD88 was present in the CNS, but not bone marrow-derived cells, mounted proinflammatory mediator expression profiles and neutrophil recruitment equivalent to or exceeding that detected in WT (wild-type) mice. These results implicate CNS MyD88 as essential in eliciting the initial wave of inflammation during the acute response to parenchymal infection. Microarray analysis of infected MyD88 KO compared with WT mice revealed a preponderance of differentially regulated genes involved in apoptotic pathways, suggesting that the extensive tissue damage characteristic of brain abscesses from MyD88 KO mice could result from dysregulated apoptosis. Collectively, the findings of the present study highlight a novel mechanism for CNS-resident cells in initiating a protective innate immune response in the infected brain and, in the absence of MyD88 in this compartment, immunity is compromised.

Original languageEnglish (US)
Article numbere00007
Pages (from-to)77-90
Number of pages14
JournalASN Neuro
Volume1
Issue number2
DOIs
StatePublished - 2009

Keywords

  • Bone marrow chimaera mice
  • Brain abscess
  • Central nervous system
  • MyD88
  • Staphylococcus aureus
  • Toll-like receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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