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Citrobacter freundii Activation of NLRP3 Inflammasome via the Type VI Secretion System

Liyun Liu1, Liqiong Song1, Rong Deng2

  • 1State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Research Units of Discovery of Unknown Bacteria and Function (2018RU010), Chinese Academy of Medical Sciences, Beijing, China.

The Journal of Infectious Diseases
|November 5, 2020
PubMed

Insights

Citrobacter freundii infections are linked to a type VI secretion system (T6SS) that activates NLRP3 inflammasomes. This T6SS mechanism is crucial for bacterial pathogenesis and host immune responses.

Area of Science:

  • Microbiology
  • Immunology
  • Bacterial Pathogenesis

Background:

  • Citrobacter freundii causes significant human infections, including food poisoning and UTIs.
  • A highly cytotoxic C. freundii strain CF74 possesses a type VI secretion system (T6SS).

Purpose of the Study:

  • To investigate the role of C. freundii T6SS in activating the NLRP3 inflammasome pathway.
  • To elucidate the mechanisms by which T6SS contributes to C. freundii pathogenesis in macrophages and in vivo.

Main Methods:

  • Macrophage activation assays using C. freundii CF74.
  • Analysis of inflammasome components (NLRP3, caspase-1) and pyroptosis markers.
  • In vivo infection models in mice to assess bacterial survival and immune responses.

Main Results:

  • C. freundii CF74 activated NLRP3 inflammasomes in a T6SS-dependent manner in macrophages.
  • The T6SS mediated pyroptosis via caspase-1 and gasdermin-N, and was essential for flagellin-induced IL-1β release.
  • The T6SS effector Hcp-2 was sufficient to trigger NLRP3 inflammasome activation.
  • In vivo, T6SS was critical for IL-1β secretion and host survival during infection.

Conclusions:

  • The T6SS of C. freundii CF74 is a key virulence factor that activates the NLRP3 inflammasome pathway.
  • T6SS-mediated pyroptosis contributes to C. freundii pathogenesis and host immune response.
  • These findings offer new insights into C. freundii infection mechanisms and host-pathogen interactions.
Keywords:
Citrobacter freundiiNLRP3T6SSinflammasome

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