Division of Infectious Diseases, Department of Pediatrics, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California 90027, USA.
Nat Commun. 2011 Nov 22;2:552. doi: 10.1038/ncomms1554.
Despite the fundamental function of neutrophils (polymorphonuclear leukocytes (PMNs)) in innate immunity, their role in Escherichia coli K1 (EC-K1) -induced meningitis is unexplored. Here we show that PMN-depleted mice are resistant to EC-K1 (RS218) meningitis. EC-K1 survives and multiplies in PMNs for which outer membrane protein A (OmpA) expression is essential. EC-K1 infection of PMNs increases the cell surface expression of gp96, which acts as a receptor for bacterial entry. Suppression of gp96 expression in newborn mice prevents the onset of EC-K1 meningitis. Infection of PMNs with EC-K1 suppresses oxidative burst by downregulating rac1, rac2 and gp91(phox) transcription both in vitro and in vivo. The interaction of loop 2 of OmpA with gp96 is essential for EC-K1-mediated inhibition of oxidative burst. These results reveal that EC-K1 exploits surface-expressed gp96 in PMNs to prevent oxidative burst for the onset of neonatal meningitis.
尽管中性粒细胞（多形核白细胞（PMN））在先天免疫中具有基本功能，但它们在大肠杆菌 K1（EC-K1）诱导的脑膜炎中的作用尚不清楚。在这里，我们表明PMN 耗竭小鼠对 EC-K1（RS218）脑膜炎具有抗性。EC-K1 在中性粒细胞中存活和繁殖，外膜蛋白 A（OmpA）的表达对其至关重要。EC-K1 感染中性粒细胞会增加 gp96 的细胞表面表达，gp96 作为细菌进入的受体发挥作用。在新生小鼠中抑制 gp96 的表达可防止 EC-K1 脑膜炎的发生。EC-K1 感染中性粒细胞会通过下调 rac1、rac2 和 gp91(phox) 的转录来抑制体外和体内的氧化爆发。OmpA 环 2 与 gp96 的相互作用对于 EC-K1 介导的氧化爆发抑制至关重要。这些结果表明，EC-K1 利用中性粒细胞表面表达的 gp96 来防止氧化爆发，从而引发新生儿脑膜炎。
