In:
The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 1_Supplement ( 2015-05-01), p. 125.3-125.3
Abstract:
Legionella pneumophila (Legionella) is the causative agent of Legionnaires’ disease. Clearance of Legionella requires efficient phagolysosomal fusion. Regulation of the host actin cytoskeleton is crucial for proper vesicle trafficking. It has been determined that activation of caspases-1/11 are required for trafficking and fusion during infection. The molecular mechanisms of caspase-mediated clearance are unknown. It is this study’s objective to decipher the effects of caspase-1/11 on actin dynamics to promote phagolysosomal fusion and restriction. During Legionella infection, caspase-1 and -11-/- macrophages exhibited diminished F/G-actin ratios compared to WT counterparts. In addition, the absence of caspase-1 or -11 prevented the colocalization of the bacterium with F-actin, inhibiting fusion. In elucidating the molecular mechanism, it was found that caspase-1 and -11 differentially distinct molecules upstream of the actin regulator cofilin. We found that the activation of cofilin was affected by both caspases distinctly to promote phagolysosomal fusion, during Legionella infection. These data establish that inflammasome caspases differentially regulate actin polymerization during Legionella infection by modulating F-actin assembly via the activation of cofilin. Understanding the novel molecular mechanisms of caspase-mediated regulation of the host cytoskeletal network will provide novel targets to develop therapeutic interventions for numerous infectious diseases.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.194.Supp.125.3
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2015
detail.hit.zdb_id:
1475085-5
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