Microglial activation by Citrobacter koseri is mediated by TLR4- and MyD88-dependent pathways

Shuliang Liu, Tammy Kielian

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Citrobacter koseri is a Gram-negative bacterium that can cause a highly aggressive form of neonatal meningitis, which often progresses to establish multifocal brain abscesses. Despite its tropism for the brain parenchyma, microglial responses to C. koseri have not yet been examined. Microglia use TLRs to recognize invading pathogens and elicit proinflammatory mediator expression important for infection containment. In this study, we investigated the importance of the LPS receptor TLR4 and MyD88, an adaptor molecule involved in the activation of the majority of TLRs in addition to the IL-1 and IL-18 receptors, for their roles in regulating microglial activation in response to C. koseri. Proinflammatory mediator release was significantly reduced in TLR4 mutant and MyD88 knockout microglia compared with wild-type cells following exposure to either live or heat-killed C. koseri, indicating a critical role for both TLR4- and MyD88-dependent pathways in microglial responses to this pathogen. However, residual proinflammatory mediator expression was still observed in TLR4 mutant and MyD88 KO microglia following C. koseri exposure, indicating a contribution of TLR4- and MyD88-independent pathway(s) for maximal pathogen recognition. Interestingly, C. koseri was capable of surviving intracellularly in both primary microglia and macrophages, suggesting that these cells may serve as a reservoir for the pathogen during CNS infections. These results demonstrate that microglia respond to C. koseri with the robust expression of proinflammatory molecules, which is dictated, in part, by TLR4- and MyD88-dependent signals.

Original languageEnglish (US)
Pages (from-to)5537-5547
Number of pages11
JournalJournal of Immunology
Issue number9
StatePublished - Nov 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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