Actin polymerization as a key innate immune effector mechanism to control Salmonella infection

Si Ming Man, Andrew Ekpenyong, Panagiotis Tourlomousis, Sarra Achouri, Eugenia Cammarota, Katherine Hughes, Alessandro Rizzo, Gilbert Ng, John A. Wright, Pietro Cicuta, Jochen R. Guck, Clare E. Bryant

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Salmonellosis is one of the leading causes of food poisoning worldwide. Controlling bacterial burden is essential to surviving infection. Nucleotide-binding oligomerization domain-like receptors (NLRs), such as NLRC4, induce inflammasome effector functions and play a crucial role in controlling Salmonella infection. Inflammasome-dependent production of IL-1β recruits additional immune cells to the site of infection, whereas inflammasomemediated pyroptosis of macrophages releases bacteria for uptake by neutrophils. Neither of these functions is known to directly kill intracellular salmonellae within macrophages. The mechanism, therefore, governing how inflammasomes mediate intracellular bacterial-killing and clearance in host macrophages remains unknown. Here, we show that actin polymerization is required for NLRC4-dependent regulation of intracellular bacterial burden, inflammasome assembly, pyroptosis, and IL-1β production. NLRC4- induced changes in actin polymerization are physically manifested as increased cellular stiffness, and leads to reduced bacterial uptake, production of antimicrobial molecules, and arrested cellular migration. These processes act in concert to limit bacterial replication in the cell and dissemination in tissues. We show, therefore, a functional link between innate immunity and actin turnover in macrophages that underpins a key host defense mechanism for the control of salmonellosis.

Original languageEnglish (US)
Pages (from-to)17588-17593
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number49
StatePublished - Dec 9 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


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