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Immune-responsiveness of CD4⁺ T cells during Streptococcus suis serotype 2 infection.

ABSTRACT: The pathogenesis of Streptococcus suis infection, a major swine and human pathogen, is only partially understood and knowledge on the host adaptive immune response is critically scarce. Yet, S. suis virulence factors, particularly its capsular polysaccharide (CPS), enable this bacterium to modulate dendritic cell (DC) functions and potentially impair the immune response. This study aimed to evaluate modulation of T cell activation during S. suis infection and the role of DCs in this response. S. suis-stimulated total mouse splenocytes readily produced TNF-?, IL-6, IFN-?, CCL3, CXCL9, and IL-10. Ex vivo and in vivo analyses revealed the involvement of CD4⁺ T cells and a Th1 response. Nevertheless, during S. suis infection, levels of the Th1-derived cytokines TNF-? and IFN-? were very low. A transient splenic depletion of CD4⁺ T cells and a poor memory response were also observed. Moreover, CD4⁺ T cells secreted IL-10 and failed to up-regulate optimal levels of CD40L and CD69 in coculture with DCs. The CPS hampered release of several T cell-derived cytokines in vitro. Finally, a correlation was established between severe clinical signs of S. suis disease and impaired antibody responses. Altogether, these results suggest S. suis interferes with the adaptive immune response.

SUBMITTER: Lecours MP

PROVIDER: S-EPMC5131321 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Immune-responsiveness of CD4<sup>+</sup> T cells during Streptococcus suis serotype 2 infection.

Lecours Marie-Pier MP Letendre Corinne C Clarke Damian D Lemire Paul P Galbas Tristan T Benoit-Biancamano Marie-Odile MO Thibodeau Jacques J Gottschalk Marcelo M Segura Mariela M

Scientific reports 20161201

The pathogenesis of Streptococcus suis infection, a major swine and human pathogen, is only partially understood and knowledge on the host adaptive immune response is critically scarce. Yet, S. suis virulence factors, particularly its capsular polysaccharide (CPS), enable this bacterium to modulate dendritic cell (DC) functions and potentially impair the immune response. This study aimed to evaluate modulation of T cell activation during S. suis infection and the role of DCs in this response. S. ...[more]

PMID: 27905502

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Project description: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.

Dataset Information

Immune-responsiveness of CD4⁺ T cells during Streptococcus suis serotype 2 infection.

Publications

Immune-responsiveness of CD4<sup>+</sup> T cells during Streptococcus suis serotype 2 infection.

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Dataset Information

Immune-responsiveness of CD4+ T cells during Streptococcus suis serotype 2 infection.

Publications

Immune-responsiveness of CD4<sup>+</sup> T cells during Streptococcus suis serotype 2 infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Immune-responsiveness of CD4⁺ T cells during Streptococcus suis serotype 2 infection.