Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with lysosomes by modulating actin polymerization.

Abstract

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.

• Authors: Anwari Akhter, Kyle Caution, Arwa Abu Khweek, Mia Tazi, Basant A Abdulrahman, Dalia H A Abdelaziz, Oliver H Voss, Andrea I Doseff, Hoda Hassan, Abul K Azad, Larry S Schlesinger, Mark D Wewers, Mikhail A Gavrilin, Amal O Amer
• Journal: Immunity (Immunity) Vol. 37 Issue 1 Pg. 35-47 (Jul 27 2012) ISSN: 1097-4180 [Electronic] United States
• PMID: 22658523 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Actin Depolymerizing Factors
• Actins
• Casp4 protein, mouse
• Caspases
• Caspases, Initiator
• Caspase 1

Topics

• Actin Depolymerizing Factors (metabolism)
• Actins (metabolism)
• Animals
• Bacteria (growth & development, immunology)
• Bacterial Infections (immunology, metabolism)
• Caspase 1 (deficiency, genetics, metabolism)
• Caspases (deficiency, genetics, metabolism)
• Caspases, Initiator
• Humans
• Lysosomes (metabolism)
• Macrophages (immunology, metabolism, microbiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Phagosomes (metabolism, microbiology)
• Phosphorylation
• Protein Multimerization