Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea.
Front Immunol. 2023 Mar 28;14:1056949. doi: 10.3389/fimmu.2023.1056949. eCollection 2023.
, 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 infection. Since lipoteichoic acid (LTA) is a representative virulence factor of , we here investigated its role in the activation of human DCs stimulated with LTA-deficient (Δ) or 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 (Δ HKSG) showed relatively higher binding and phagocytic activities than those treated with heat-killed wild-type (wild-type HKSG). Furthermore, Δ 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 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 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 but rather it interferes with bacteria-induced DC maturation, suggesting its potential role in immune evasion.
金黄色酿脓葡萄球菌是一种机会性革兰氏阳性菌，可引起感染性心内膜炎，对人类健康构成致命威胁。树突状细胞（DC）被认为参与了 感染的疾病进展和免疫反应。由于脂磷壁酸（LTA）是金黄色酿脓葡萄球菌的代表性毒力因子，我们在此研究了其在LTA 缺陷（Δ）或野生型 金黄色酿脓葡萄球菌（LTA）刺激的人树突状细胞激活中的作用。在 GM-CSF 和 IL-4 的存在下，从人血液衍生的单核细胞中分化出 DC 细胞，持续 6 天。与热灭活野生型金黄色酿脓葡萄球菌（野生型 HKSG）相比，用热灭活 Δ金黄色酿脓葡萄球菌（Δ HKSG）处理的 DC 显示出相对更高的结合和吞噬活性。此外，与野生型 HKSG 相比，Δ HKSG 在诱导表型成熟标志物（包括 CD80、CD83、CD86、PD-L1 和 PD-L2、抗原呈递分子 MHC Ⅱ类和促炎细胞因子如 TNF-α和 IL-6）方面更具优势。同时，与用野生型处理的 DC 相比，用 Δ HKSG 处理的 DC 诱导更好的 T 细胞活性，包括增殖和激活标志物（CD25）的表达。从 中分离出的 LTA，但不是脂蛋白，可弱激活 TLR2，几乎不影响 DC 中表型成熟标志物或细胞因子的表达。总之，这些结果表明 LTA 不是 金黄色酿脓葡萄球菌的主要免疫刺激剂，而是干扰细菌诱导的 DC 成熟，表明其在免疫逃避中的潜在作用。
