Abstract
Streptococcus suis is an important swine pathogen and emerging zoonotic agent. Encapsulated strains of S. suis modulate dendritic cell (DC) functions, leading to poorly activated CD4+ T cells. However, the antigen presentation ability of S. suis-stimulated DCs has not been investigated yet. In this work, we aimed to characterize the antigen presentation profiles of S. suis-stimulated DCs, both in vitro and in vivo. Upon direct activation in vitro, S. suis-stimulated murine bone marrow-derived DCs (bmDCs) preserved their antigen capture/processing capacities. However, they showed delayed kinetics of MHC-II expression compared to lipopolysaccharide-stimulated bmDCs. Meanwhile, splenic DCs from infected mice exhibited a compromised MHC-II expression, despite an appropriate expression of maturation markers. To identify potential interfering mechanisms, Class II Major Histocompatibility Complex Transactivator (CIITA) and membrane-associated RING-CH (MARCH)1/8 transcription were studied. S. suis-stimulated DCs maintained low levels of CIITA at early time points, both in vitro and in vivo, which could limit their ability to increase MHC-II synthesis. S. suis-stimulated DCs also displayed sustained/upregulated levels of MARCH1/8, thus possibly leading to MHC-II lysosomal degradation. The bacterial capsular polysaccharide played a partial role in this modulation. Finally, interleukin (IL)-12p70 production was inhibited in splenic DCs from infected mice, a profile compatible with DC indirect activation by pro-inflammatory compounds. Consequently, these cells induced lower levels of IL-2 and TNF-α in an antigen-specific CD4+ T cell presentation assay and blunted T cell CD25 expression. It remains unclear at this stage whether these phenotypical and transcriptional modulations observed in response to S. suis in in vivo infections are part of a bacterial immune evasion strategy or rather a feature common to systemic inflammatory response-inducing agents. However, it appears that the MHC-II-restricted antigen presentation and Th1-polarizing cytokine production capacities of DCs are impaired during S. suis infection. This study highlights the potential consequences of inflammation on the type and magnitude of the immune response elicited by a pathogen.
Highlights
Streptococcus suis is one of the most important bacterial pathogens in pigs causing meningitis, septicemia, and sudden death [1]
LPS-treated bone marrow-derived dendritic cell (bmDC) served as positive controls for the expected kinetics of MHC-II expression in bmDCs responding to a Toll-like receptor (TLR) ligand
A statistically significant difference was observed between the two strains at 4 h, suggesting that the presence of the capsular polysaccharides (CPS) on S. suis plays a partial role in the delayed maturation process underwent by S. suis-stimulated bmDCs
Summary
Streptococcus suis is one of the most important bacterial pathogens in pigs causing meningitis, septicemia, and sudden death [1]. It is responsible for major economic losses to the swine industry worldwide, and yet there is currently no real effective vaccine available to control infections caused by this bacterium [2]. Serotype 2 is the most virulent for both pigs and humans, and most studies have been performed with this serotype [1]. S. suis possesses several virulence factors [6], among which the CPS is clearly critical for the pathogenesis of S. suis infections [7]
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