Abstract

Dendritic cells (DCs) play a pivotal role in the induction of immunity by recognition, capture, process, and presentation of antigens from infectious microbes. Streptococcus gordonii is able to cause life-threatening systemic diseases such as infective endocarditis. Serine-rich repeat (SRR) glycoproteins of S. gordonii are sialic acid-binding adhesins mediating the bacterial adherence to the host and the development of infective endocarditis. Thus, the SRR adhesins are potentially involved in the bacterial adherence to DCs and the maturation and activation of DCs required for the induction of immunity to S. gordonii. Here, we investigated the phenotypic and functional changes of human monocyte-derived DCs treated with wild-type S. gordonii or the SRR adhesin-deficient mutant. The mutant poorly bound to DCs and only weakly increased the expression of CD83, CD86, MHC class II, and PD-L1 on DCs compared with the wild-type. In addition, the mutant induced lower levels of TNF-α, IL-6, and IL-12 than the wild-type in DCs. When DCs sensitized with the mutant were co-cultured with autologous T cells, they induced weaker proliferation and activation of T cells than DCs stimulated with the wild-type. Blockade of SRR adhesin with 3′-sialyllactose markedly reduced S. gordonii binding and internalization, causing attenuation of the bacterial immunostimulatory potency in DC maturation. Collectively, our results suggest that SRR adhesins of S. gordonii are important for maturation and activation of DCs.

Highlights

  • Streptococcus gordonii is a Gram-positive facultative anaerobic bacterium belonging to the viridans group of oral streptococci (Loo et al, 2000)

  • The results indicate that serine-rich repeat (SRR) adhesins Hsa and GspB are crucial for the adherence and internalization of S. gordonii to dendritic cells (DCs)

  • We demonstrated that S. gordonii lacking SRR adhesins showed marked reduction in DC maturation, production of inflammatory cytokines, and T cell-activating ability compared to wild-type S. gordonii

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Summary

Introduction

Streptococcus gordonii is a Gram-positive facultative anaerobic bacterium belonging to the viridans group of oral streptococci (Loo et al, 2000). S. gordonii preferentially binds to human platelets, causing their aggregation, facilitating bacterial colonization in the endocardium and DC Maturation by S. gordonii heart valves and resulting in endocarditis (Takahashi et al, 2006). Previous studies have shown that oral streptococci associated with endocarditis promote rapid differentiation of monocytes into mature dendritic cells (DCs) (Hahn et al, 2005) and S. gordonii induces the secretion of cytokines including TNFα, IL-6, and IL-12 in DCs (Corinti et al, 1999), implying the importance of DCs in the disease development and immune responses. S. gordonii adheres to sialic acids on platelets or erythrocytes through SRR adhesins in injured heart valves, exacerbating inflammatory responses by promoting deposition of bacteriumplatelet-fibrin complexes and recruiting inflammatory immune cells in tissues (Yajima et al, 2008)

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