Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with lysosomes by modulating actin polymerization.
Inflammasomes are multiprotein complexes that include members of the NLR (nucleotide-binding domain leucine-rich repeat containing) family and caspase-1. Once bacterial molecules are sensed within the macrophage, the inflammasome is assembled, mediating the activation of caspase-1. Caspase-11 mediates caspase-1 activation in response to lipopolysaccharide and bacterial toxins, and yet its role during bacterial infection is unknown. Here, we demonstrated that caspase-11 was dispensable for caspase-1 activation in response to Legionella, Salmonella, Francisella, and Listeria. We also determined that active mouse caspase-11 was required for restriction of L. pneumophila infection. Similarly, human caspase-4 and caspase-5, homologs of mouse caspase-11, cooperated to restrict L. pneumophila infection in human macrophages. Caspase-11 promoted the fusion of the L. pneumophila vacuole with lysosomes by modulating actin polymerization through cofilin. However, caspase-11 was dispensable for the fusion of lysosomes with phagosomes containing nonpathogenic bacteria, uncovering a fundamental difference in the trafficking of phagosomes according to their cargo.
Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA.
Anwari
A
Akhter
Kyle
K
Caution
Arwa
A
Abu Khweek
Mia
M
Tazi
Basant A
BA
Abdulrahman
Dalia H A
DH
Abdelaziz
Oliver H
OH
Voss
Andrea I
AI
Doseff
Hoda
H
Hassan
Abul K
AK
Azad
Larry S
LS
Schlesinger
Mark D
MD
Wewers
Mikhail A
MA
Gavrilin
Amal O
AO
Amer
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001419:Bacteria / Q000254:growth & development / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism; D020170:Caspase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053471:Caspases, Initiator; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010588:Phagosomes / Q000378:metabolism* / Q000382:microbiology; D010766:Phosphorylation; D055503:Protein Multimerization
D051339:Actin Depolymerizing Factors; D000199:Actins; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator; D020170:Caspase 1