Subversion of antimicrobial calprotectin (S100A8/S100A9 complex) in the cytoplasm of TR146 epithelial cells after invasion by Listeria monocytogenes

A. A. Zaia, K. J. Sappington, K. Nisapakultorn, W. J. Chazin, E. A. Dietrich, K. F. Ross, M. C. Herzberg

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Expressed by squamous mucosal keratinocytes, calprotectin is a complex of two EF-hand calcium-binding proteins of the S100 subfamily (S100A8 and S100A9) with significant antimicrobial activity. Calprotectin-expressing cells resist invasion by Porphyromonas gingivalis, Listeria monocytogenes, and Salmonella enterica serovar Typhimurium (S. typhimurium). To understand the interactions between calprotectin and invasive bacteria, we studied the distribution of calprotectin in the cytoplasm of TR146 epithelial cells. In response to L. monocytogenes, calprotectin mobilized from a diffuse cytoplasmic distribution to a filamentous pattern and colocalized with the microtubule network. Listeria more frequently invaded cells with mobilized calprotectin. Calprotectin mobilization was listeriolysin O-dependent and required calcium (extracellular and intracellular) and an intact microtubule network. In the presence of preformed microtubules in vitro, the anti-Listeria activity of calprotectin was abrogated. To facilitate intraepithelial survival, therefore, Listeria mobilizes calprotectin to colocalize with cytoplasmic microtubules, subverting anti-Listeria activity and autonomous cellular immunity.

Original languageEnglish (US)
Pages (from-to)43-53
Number of pages11
JournalMucosal Immunology
Volume2
Issue number1
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
This study was supported by NIH grants RO1DE11831, P30DE09737 and RO1GM62112. Alexandre A Zaia also was supported by FAPESP from Brazil, grant 99 / 10079-4. Kanokwan Nisapakultorn was supported by a scholarship from The Royal Thai government. We thank James Hodges and Joel Rudney for assistance with the statistical analysis and Roy Curtiss, Daniel Portnoy, and Darren Higgins for supplying bacterial strains and mutants used in this study.

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