Rôle essentiel des cellules dendritiques dans l'immunité innée face a des streptocoques encapsulés
Group B Streptococcus (GBS) and Streptococcus suis are two encapsulated pathogens that induce similar pathologies, including septicemia and meningitis in animals and/or humans. Serotypes III and V of GBS and serotypes 2 and 14 of S. suis  (evaluated in this study) are the most prevalent and/or virulent types. The capsular polysaccharide (CPS) defines the serotype and is considered as a key virulence factor for both bacterial species.  Although several studies have addressed the interactions of these streptococci and various cells of the innate immune system, no information is available on the regulation of the immune response against these pathogens by dendritic cells (DCs), and their interactions with other cells, including natural killer (NK) cells. In this study, different approaches (in vitro, ex vivo and in vivo) in mice were developed to characterize the interactions between DCs, NK cells and GBS or S. suis. Non-encapsulated mutants were used to evaluate the importance of the CPS in these interactions.  In vitro results with GBS- or S. suis-infected DCs showed that these two pathogens differently interact with these cells. GBS is largely internalized by DCs through multiple endocytosis mechanisms, mainly involving lipid rafts and clathrin. The use of a specific endocytosis pathway might help GBS to survive intracellularly. In contrast, S. suis is poorly internalized and, if the case, rapidly eliminated within the DCs. GBS and S. suis activate DCs through different receptors leading to the release of cytokines and chemokines and increased expression of co-stimulatory molecules. This activation allows the production of IFN- by NK cells. Yet, S. suis capacity to activate DCs and NK cells is lower than that observed for GBS. IFN- release in response to bacterial stimulation was mainly mediated by direct DC-NK cell contact and only partially dependant on soluble factors. In addition, our in vivo results showed that these two streptococcal species rapidly induce the release of IFN- by NK cells during the acute phase of the infection. This suggests that the DC-NK crosstalk might play a role in the development of a T helper 1 (Th1) response. Yet, S. suis capacity to activate the in vivo immune response was also lower than that observed for GBS. In fact, GBS and S. suis CPSs play different roles in this response. S. suis CPS prevents optimal activation of DCs and NK cells whereas it is the opposite for GBS, independently of the serotype tested.   In summary, this study addresses for the first time the contribution of DCs and NK cells to the innate immune response against GBS and S. suis infections, and by extension, to the development of a Th1 response. Our results further highlight the central role of DCs in the effective control of infections caused by encapsulated bacteria.
Streptococcus suis Cellules natural killer Cytokines Group B Streptococcus Capsular polysaccharide Dendritic cells Natural killer cells Mice Th1 response Endocytosis Receptors