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

ABSTRACTCASP4/ caspase-11-dependent inflammasomeactivation 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 phagosomesharboring intracellular pathogens such as Legionella pneumophilabut 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 autophagosomeformation in response to B. cenocepacia infection. The absence of CASP4 causes an accumulation of the small GTPaseRAB7, reduced colocalizationof B. cenocepacia with LC3 and acidic compartments accompanied by increased bacterial replication in vitro and in vivo. Together, our data reveal...