Streptococcus suis Capsular Polysaccharide Inhibits Phagocytosis through Destabilization of Lipid Microdomains and Prevents Lactosylceramide-Dependent Recognition
Streptococcus suis Capsular Polysaccharide Inhibits Phagocytosis through Destabilization of Lipid Microdomains and Prevents Lactosylceramide-Dependent Recognition
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DOI：
10.1128/iai.05734-11
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发表时间：
2012-02-01
影响因子：
3.1
通讯作者：
Segura, Mariela
中科院分区：
文献类型：
--
作者：
Houde, Mathieu;Gottschalk, Marcelo;Segura, Mariela
猪链球菌2型是猪的主要病原体，也是人畜共患病的病原体，可引起猪和人的脑膜炎。猪链球菌通过呼吸道感染宿主，到达血液，并持续到侵入中枢神经系统。猪链球菌2型衣壳多糖(CPS)被认为是该细菌的关键毒力因子。虽然CPS允许猪链球菌附着在免疫系统的细胞膜上，但它提供了防止吞噬的保护。事实上，未被包膜的突变体很容易被巨噬细胞和树突状细胞内化和杀死。本工作的目的是研究猪链球菌CPS抑制吞噬作用的分子机制。通过使用与纯化的CPS共价连接的乳胶球，证明CPS本身足以抑制乳胶球和旁观者荧光球进入巨噬细胞。与巨噬细胞接触时，微囊化猪链球菌可破坏细胞表面脂质微区的稳定性，阻断感染期间一氧化氮(NO)的产生，并防止感染期间乳糖基神经酰胺在吞噬杯中积聚。相比之下，未被包裹的突变体很容易通过脂筏以非利培林敏感的方式内化，导致乳糖基神经酰胺的募集和强烈的NO产生。这是第一次发现CPS在脂质微域稳定性中的作用，并认识到吞噬细胞中猪链球菌和乳糖基神经酰胺之间的相互作用。
Streptococcus suis type 2 is a major swine pathogen and a zoonotic agent, causing meningitis in both swine and humans. S. suis infects the host through the respiratory route, reaches the bloodstream, and persists until breaching into the central nervous system. The capsular polysaccharide (CPS) of S. suis type 2 is considered a key virulence factor of the bacteria. Though CPS allows S. suis to adhere to the membrane of cells of the immune system, it provides protection against phagocytosis. In fact, non-encapsulated mutants are easily internalized and killed by macrophages and dendritic cells. The objective of this work was to study the molecular mechanisms by which the CPS of S. suis prevents phagocytosis. By using latex beads covalently linked with purified CPS, it was shown that CPS itself was sufficient to inhibit entry of both latex beads and bystander fluorescent beads into macrophages. Upon contact with macrophages, encapsulated S. suis was shown to destabilize lipid microdomains at the cell surface, to block nitric oxide (NO) production during infection, and to prevent lactosylceramide accumulation at the phagocytic cup during infection. In contrast, the nonencapsulated mutant was easily internalized via lipid rafts, in a filipin-sensitive manner, leading to lactosylceramide recruitment and strong NO production. This is the first report to identify a role for CPS in lipid microdomain stability and to recognize an interaction between S. suis and lactosylceramide in phagocytes.