State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, China.
Infect Immun. 2021 Apr 16;89(5). doi: 10.1128/IAI.00696-20.
Siglecs are sialic acid-binding immunoglobulin-like lectins that play an important role in tissue homeostasis, immune response, and pathogen infection. Bacterial sialidases act on natural ligands of Siglecs, interfering with the Siglec-mediated immune response. is a porcine bacterial pathogen that secretes sialidase. However, little is known about the sialidase of and its impact on immune regulation. Here, we used wild-type , a sialidase-deficient mutant, and complementary strains to investigate the role of sialidase in porcine alveolar macrophage infection. Sialidase induced the release of proinflammatory cytokines, such as interleukin-1α (IL-1α), IL-6, and tumor necrosis factor alpha, from porcine alveolar macrophages. Moreover, sialidase desialylated the surface of porcine alveolar macrophages and altered the expression of Siglecs (the expression of Siglec-5 was reduced). Furthermore, sialidase led to a reduction in endogenous SH2 domain-containing protein tyrosine phosphatase (SHP-2) recruitment to Siglec-5 and simultaneously activated the inflammatory response via the mitogen-activated protein kinase and nuclear factor kappa light chain enhancer of activated B cell signaling pathways. This desialylation occurred before the release of proinflammatory cytokines, suggesting that the sialidase-induced inflammatory response was followed by reduced recruitment of SHP-2 to Siglec-5. Thus, this study is the first to demonstrate the role of sialidase in the inflammatory response of This role resulted from the abrogation of negative regulation of Siglec-5 on proinflammatory cytokine release. This study helps to understand the molecular mechanism underlying the inflammatory response induced by sialidase secreted by and the acute inflammation caused by .
唾液酸结合免疫球蛋白样凝集素（Siglecs）是一类重要的免疫调节分子，在组织稳态、免疫反应和病原体感染中发挥重要作用。细菌唾液酸酶作用于 Siglecs 的天然配体，干扰 Siglec 介导的免疫反应。 是一种猪源细菌病原体，可分泌唾液酸酶。然而，关于 的唾液酸酶及其对免疫调节的影响知之甚少。在这里，我们使用野生型 、唾液酸酶缺陷突变株和互补株来研究唾液酸酶在猪肺泡巨噬细胞感染中的作用。唾液酸酶诱导猪肺泡巨噬细胞释放促炎细胞因子，如白细胞介素-1α（IL-1α）、IL-6 和肿瘤坏死因子-α。此外，唾液酸酶使猪肺泡巨噬细胞表面去唾液酸化，并改变 Siglecs 的表达（Siglec-5 的表达减少）。此外，唾液酸酶导致内源性含 SH2 结构域的蛋白酪氨酸磷酸酶（SHP-2）向 Siglec-5 的募集减少，并通过丝裂原活化蛋白激酶和核因子 kappa B 轻链增强子的激活 B 细胞信号通路同时激活炎症反应。这种去唾液酸化发生在促炎细胞因子释放之前，表明唾液酸酶诱导的炎症反应伴随着 Siglec-5 向 SHP-2 的募集减少。因此，本研究首次证明了唾液酸酶在 引起的炎症反应中的作用。这种作用是由于 Siglec-5 对促炎细胞因子释放的负调控作用被阻断所致。本研究有助于理解 分泌的唾液酸酶引起的炎症反应以及 引起的急性炎症的分子机制。
