CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection

Kathrin Krause, Kyle Caution, Asmaa Badr, Kaitlin Hamilton, Abdulmuti Saleh, Khushbu Patel, Stephanie Seveau, Luanne Hall-Stoodley, Rana Hegazi, Xiaoli Zhang, Mikhail A. Gavrilin, Amal O. Amer

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

CASP4/caspase-11-dependent inflammasome activation is important for the clearance of various Gram-negative bacteria entering the host cytosol. Additionally, CASP4 modulates the actin cytoskeleton to promote the maturation of phagosomes harboring intracellular pathogens such as Legionella pneumophila but not those enclosing nonpathogenic bacteria. Nevertheless, this non-inflammatory role of CASP4 regarding the trafficking of vacuolar bacteria remains poorly understood. Macroautophagy/autophagy, a catabolic process within eukaryotic cells, is also implicated in the elimination of intracellular pathogens such as Burkholderia cenocepacia. Here we show that CASP4-deficient macrophages exhibit a defect in autophagosome formation in response to B. cenocepacia infection. The absence of CASP4 causes an accumulation of the small GTPase RAB7, reduced colocalization of B. cenocepacia with LC3 and acidic compartments accompanied by increased bacterial replication in vitro and in vivo. Together, our data reveal a novel role of CASP4 in regulating autophagy in response to B. cenocepacia infection.

Original languageEnglish (US)
Pages (from-to)1928-1942
Number of pages15
JournalAutophagy
Volume14
Issue number11
DOIs
Publication statusPublished - Nov 2 2018

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Keywords

  • autophagy
  • Burkholderia cenocepacia
  • caspase-1 (CASP1)
  • caspase-11 (CASP4)
  • lysosome
  • macrophages

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Krause, K., Caution, K., Badr, A., Hamilton, K., Saleh, A., Patel, K., ... Amer, A. O. (2018). CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection. Autophagy, 14(11), 1928-1942. https://doi.org/10.1080/15548627.2018.1491494