Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.
Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Front Immunol. 2019 May 7;10:1012. doi: 10.3389/fimmu.2019.01012. eCollection 2019.
is a stealthy intracellular bacterial pathogen of animals and humans. This bacterium promotes the premature cell death of neutrophils (PMN) and resists the killing action of these leukocytes. -infected PMNs presented phosphatidylserine (PS) as "eat me" signal on the cell surface. This signal promoted direct contacts between PMNs and macrophages (Mϕs) and favored the phagocytosis of the infected dying PMNs. Once inside Mϕs, replicated within Mϕs at significantly higher numbers than when Mϕs were infected with bacteria alone. The high levels of the regulatory IL-10 and the lower levels of proinflammatory TNF-α released by the -PMN infected Mϕs, at the initial stages of the infection, suggested a non-phlogistic phagocytosis mechanism. Thereafter, the levels of proinflammatory cytokines increased in the -PMN-infected Mϕs. Still, the efficient bacterial replication proceeded, regardless of the cytokine levels and Mϕ type. Blockage of PS with Annexin V on the surface of -infected PMNs hindered their contact with Mϕs and hampered the association, internalization, and replication of within these cells. We propose that infected PMNs serve as "Trojan horse" vehicles for the efficient dispersion and replication of the bacterium within the host.
是一种潜伏的动物和人类细胞内细菌病原体。这种细菌促进中性粒细胞(PMN)过早死亡,并抵抗这些白细胞的杀伤作用。感染的 PMN 表面呈现出磷脂酰丝氨酸(PS)作为“吃我”信号。这种信号促进了 PMN 和巨噬细胞(Mϕ)之间的直接接触,并有利于感染的死亡 PMN 的吞噬作用。一旦进入 Mϕ 内,在 Mϕ 内的复制数量明显高于 Mϕ 单独感染细菌时的数量。在感染的初始阶段,由感染的 PMN 释放的调节性 IL-10 水平较高和促炎 TNF-α 水平较低表明存在非炎症性吞噬作用机制。此后,感染的 PMN 中促炎细胞因子的水平增加。尽管如此,细菌的有效复制仍在继续,而与细胞因子水平和 Mϕ 类型无关。用 Annexin V 阻断感染的 PMN 表面的 PS 会阻碍它们与 Mϕ 的接触,并阻碍它们之间的关联、内化和复制。我们提出,感染的 PMN 作为“特洛伊木马”载体,可在宿主内有效分散和复制细菌。