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

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 <i>Legionella pneumophila</i> 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 <i>Burkholderia cenocepacia</i>. Here we show that CASP4-deficient macrophages exhibit a defect in autophagosome formation in response to <i>B. cenocepacia</i> infection. The absence of CASP4 causes an accumulation of the small GTPase RAB7, reduced colocalization of <i>B. cenocepacia</i> with LC3 and acidic compartments accompanied by increased bacterial replication <i>in vitro</i> and <i>in vivo</i>. Together, our data reveal a novel role of CASP4 in regulating autophagy in response to <i>B. cenocepacia</i> infection.