Internalization of staphylococcal leukotoxins that bind and divert the C5a receptor is required for intracellular Ca(2+) mobilization by human neutrophils - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cellular Microbiology Année : 2015

Internalization of staphylococcal leukotoxins that bind and divert the C5a receptor is required for intracellular Ca(2+) mobilization by human neutrophils

Résumé

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 Staphylococcus 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.

Dates et versions

hal-02933964 , version 1 (08-09-2020)

Identifiants

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Mira Tawk, Gaëlle Zimmermann - Meisse, Jean-Louis Bossu, Cristina Potrich, Tristan Bourcier, et al.. Internalization of staphylococcal leukotoxins that bind and divert the C5a receptor is required for intracellular Ca(2+) mobilization by human neutrophils. Cellular Microbiology, 2015, 17 (8), pp.1241-1257. ⟨10.1111/cmi.12434⟩. ⟨hal-02933964⟩

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