INDIRECT ACTIVATION OF DENDRITIC CELLS DURING STREPTOCOCCUS SUIS SEROTYPE 2 INFECTION IN A MURINE MODEL
Corinne Letendre, University of Montreal
Corinne Letendre1, Jean-Philippe Auger2, Marcelo Gottschalk2, Jacques Thibodeau3, Mariela
1. Laboratory of Immunology, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, QC, Canada
2. Laboratory of Streptococcus suis, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, QC, Canada
3. Laboratory of Molecular Immunology, Department of Microbiology, Infectiology and Immunology, University of Montreal, Montreal, QC, Canada
Streptococcus suis is an important swine pathogen and emerging zoonotic agent, for which there
is still no effective vaccine available. This bacterium causes acute systemic infections
characterized by high levels of pro-inflammatory mediators. Inflammatory conditions such as
sepsis can lead to indirectly activated DCs with impaired antigen presentation capacities.
Interestingly, S. suis is known to modulate dendritic cell (DC) functions and interfere with CD4+
T cell activation. Here, we report the antigen presentation profile of splenic DCs during a systemic
infection in a murine model. Splenic DCs obtained from S. suis-infected mice showed expression
profiles of CD86/MHC-II and transcription levels of CIITA and MARCH1/8 that were compatible
with indirect activation of DCs. Moreover, the IL-12 production capacity of these cells was
impaired in an ex vivo assay, while production of other cytokines remained unaffected. Infected
splenic DCs also failed to induce the production of the Th1-derived cytokines IL-2 and TNF-alpha
in an ex vivo antigen-specific CD4+ T cell presentation assay. Hence, we conclude that S. suis
infection leads, at least partly, to indirect activation of DCs. These cells have an impaired MHCII-
restricted antigen presentation capacity and produce limited amounts of IL-12, the main Th1-
polarizing cytokine. As Th1-type responses have been associated with host protection against S.
suis, this mode of DC activation might interfere with the development of an appropriate response.
This study highlights the potential consequences of inflammation on the type and magnitude of
the immune response elicited by a pathogen