AutoriTawk, M and Zimmermann-Meisse, G and Bossu, J-L , Potrich, C. , Boucier,T., Dalla Serra, M., Poulain,B. ,Gilles Prévost and Emmanuel Jover
AbstractA 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 aureusPanton-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 Ca2+. HlgC/HlgB requires the presence of robust intracellular acidic Ca2+ stores in order to evoke a rise in free [Ca2+](i), while the LukS-PV/LukF-PV directly altered reticular Ca2+ 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 [Ca2+](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.
RivistaCellular Microbiology (print)
Impact factor0
Pagina inizio1241
Pagina fine1257
Linee di Ricerca IBFMD.P01.028.001