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

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)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.214353NIH [RO1DE11831, P30DE09737, RO1GM62112]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The Royal Thai governmentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)NIH [RO1DE11831, P30DE09737, RO1GM62112]FAPESP [99/10079-4