Internalization of staphylococcal leukotoxins that bind and divert the C5a receptor is required for intracellular Ca2+ mobilization by human neutrophils. (30th March 2015)

• Record Type: Journal Article
• Authors: Tawk, Mira Y.; Zimmermann, Kiran; Bossu, Jean‐Louis; Potrich, Cristina; Bourcier, Tristan; Dalla Serra, Mauro; Poulain, Bernard; Prévost, Gilles; Jover, Emmanuel
• Is Part Of: Cellular microbiology. Volume 17:Number 8(2015:Aug.)
• Page Start: 1241
• Page End: 1257
• Publication Date: 2015-03-30
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12434
• Languages: English
• ISSNs: 1462-5814

Abstract

Summary: A growing number of receptors, often associated with the innate immune response, are being identified as targets for bacterial toxins of the beta‐stranded pore‐forming family. These findings raise the new question of whether the receptors are activated or merely used as docking points facilitating the formation of a pore. To elucidate whether the S taphylococcus aureus Panton‐Valentine leukocidin and the leukotoxin HlgC/HlgB act through the C5a receptor (C5aR) as agonists, antagonists or differ from the C5a complement‐derived peptide, their activity is explored on C5aR‐expressing cells. Both leukotoxins equally bound C5aR in neutrophils and in stable transfected U937 cells and initiated mobilization of intracellular Ca 2+ . HlgC/HlgB requires the presence of robust intracellular acidic Ca 2+ stores in order to evoke a rise in free [Ca 2+ ]i, while the LukS‐PV/LukF‐PV directly altered reticular Ca 2+ stores. Intracellular target specificity is conferred by the F‐subunit associated to the S‐subunit binding the receptor. Furthermore, internalization of the two leukotoxin components (S‐ and F‐subunits) associated to C5aR is required for the initiation of [Ca 2+ ]i mobilization. Electrophysiological recordings on living cells demonstrated that LukS‐PV/LukF‐PV does not alter the membrane resistance of C5aR‐expressing cells. The present observations suggest that part of the pore‐forming process occurs in distinct intracellular compartments rather than at the plasma membrane.