AUTHOR=Kim Sun Kyung , Im Jintaek , Ko Eun Byeol , Lee Dongwook , Seo Ho Seong , Yun Cheol-Heui , Han Seung Hyun 

TITLE=Lipoteichoic acid of Streptococcus gordonii as a negative regulator of human dendritic cell activation

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1056949

DOI=10.3389/fimmu.2023.1056949

ISSN=1664-3224

ABSTRACT=<p><italic>Streptococcus gordonii</italic>, an opportunistic Gram-positive bacterium, causes an infective endocarditis that could be fatal to human health. Dendritic cells (DCs) are known to be involved in disease progression and immune responses in <italic>S. gordonii</italic> infection. Since lipoteichoic acid (LTA) is a representative virulence factor of <italic>S. gordonii</italic>, we here investigated its role in the activation of human DCs stimulated with LTA-deficient (Δ<italic>ltaS</italic>) <italic>S. gordonii</italic> or <italic>S. gordonii</italic> LTA. DCs were differentiated from human blood-derived monocytes in the presence of GM-CSF and IL-4 for 6 days. DCs treated with heat-killed Δ<italic>ltaS S. gordonii</italic> (Δ<italic>ltaS</italic> HKSG) showed relatively higher binding and phagocytic activities than those treated with heat-killed wild-type <italic>S. gordonii</italic> (wild-type HKSG). Furthermore, Δ<italic>ltaS</italic> HKSG was superior to wild-type HKSG in inducing phenotypic maturation markers including CD80, CD83, CD86, PD-L1, and PD-L2, antigen-presenting molecule MHC class II, and proinflammatory cytokines such as TNF-α and IL-6. Concomitantly, DCs treated with the Δ<italic>ltaS</italic> HKSG induced better T cell activities, including proliferation and activation marker (CD25) expression, than those treated with the wild-type. LTA, but not lipoproteins, isolated from <italic>S. gordonii</italic> weakly activated TLR2 and barely affected the expression of phenotypic maturation markers or cytokines in DCs. Collectively, these results demonstrated that LTA is not a major immuno-stimulating agent of <italic>S. gordonii</italic> but rather it interferes with bacteria-induced DC maturation, suggesting its potential role in immune evasion.</p>