A New Twist in the Regulation of Legionella Replication through ASC and Caspase-1

Gabriel Núñez,Luigi Franchi

doi:10.3389/fmicb.2011.00057

Gabriel Núñez, Luigi Franchi

Open Access

https://doi.org/10.3389/fmicb.2011.00057

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Abstract

A New Twist in the Regulation of Legionella Replication through ASC and Caspase-1

Highlights

Legionella pneumophila (Legionella) is a Gram-negative facultative intracellular bacterium which causes an acute form of pneumonia called Legionnaires’ disease
As Legionella does not induce caspase-1 activation in human monocytes, Amer et al (2006) assessed whether ASC was involved in restricting Legionella replication independent of its role on caspase-1 and found that depletion of ASC by siRNA promoted activation of NF-κB and enhanced bacterial growth in human monocytes
The authors provided evidence that ASCdeficient macrophages can still induce caspase-1 activation, albeit to a greatly reduced extent. Their results support the existence of a minor NLRC4-dependent, ASC-independent pathway of caspase-1 activation that is sufficient to promote the fusion of the Legionella-containing vacuoles (LCV) to the lysosomes leading to inhibition of bacterial replication

Summary

Introduction

Legionella pneumophila (Legionella) is a Gram-negative facultative intracellular bacterium which causes an acute form of pneumonia called Legionnaires’ disease. NLRC4-dependent caspase-1 activation was found to restrict the intracellular growth of Legionella, at least in part, by promoting the fusion of the LCV with lysosomes (Amer et al, 2006). The regulation of intracellular Legionella growth by the NLRC4 inflammasome is independent of IL-1β and IL-18, but relies on caspase-7, another protein substrate of caspase-1 (Akhter et al, 2009).

Results

Conclusion