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, 2010). Our data suggest that despite caveolin-1 colocalization with GBS (Fig.?3A), caveolae formation is not essential for GBS internalization by DCs. Indeed, M��CD-cholesterol depletion in CAV-1 KO bmDCs suggests that a caveolin-independent but lipid raft-dependent pathway is involved in encapsulated GBS up-take by DCs. We cannot, however, rule out the possibility that in normal DCs internalization occurs through both caveolae and lipid rafts, but in absence of caveolin the internalization is directed through lipid rafts only. Redundancy is a common event in many Gram+ pathogens (Bonazzi and Cossart, 2006). Altogether, our results suggest that GBS uses multiple endocytosis mechanisms to entry DCs and CPS seems to selectively drive bacteria http://www.selleckchem.com/screening/pfizer-licensed-library.html through different pathways. Therefore, encapsulated GBS is internalized by DCs via lipid raft-dependent http://www.selleckchem.com/products/pifithrin-alpha.html pathways, with minor implication of clathrin-mediated endocytosis. In the absence of CPS, non-encapsulated GBS fails to engage lipid raft-dependent pathways and its entry into DCs is partially driven by clathrin-mediated endocytosis. Other compensatory pathways might also be involved, including phagocytosis and constitutive non-clathrin endocytosis pathways (Doherty and McMahon, 2009). Among several cytokines tested (Lemire et?al., 2012), encapsulated GBS induced significantly higher levels of CCL2 production than the ��cpsE mutant (Fig.?3B), suggesting that CPS components might specifically contribute to CCL2 activation. Caveolin may function as a scaffolding protein to organize and concentrate inactive signalling molecules for regulated activation by appropriate receptors and to facilitate crosstalk between distinct signalling cascades (Liu et?al., 2002). Furthermore, the protein caveolin-1 itself can be tyrosine phosphorylated during certain signalling events (Duncan et?al., 2002). These observations http://en.wikipedia.org/wiki/Temsirolimus prompt us to test the hypothesis that encapsulated GBS modulates CCL2 production by caveolin-1 signalling while being internalized through lipid rafts. To this aim, we compared cytokine production induced by GBS infection of CAV-1 KO bmDCs. Among nine cytokines tested (see Experimental procedures ), CCL2 was the only one significantly affected by the absence of caveolin-1 (Fig.?3B). Indeed, a 40% inhibition of CCL2 production induced by encapsulated WT GBS was observed after infection of CAV-1 KO bmDCs compared with control bmDCs (P?