具有肠致病性大肠杆菌和溃疡性结肠炎(UC)的柠檬酸杆菌啮齿动物模型感染。当C57BL/6(C57)小鼠恢复时,C3H/HeN(C3H)小鼠死于感染,部分原因是结肠中性粒细胞弹性蛋白酶活性增加,也见于UC患者;然而,根本原因未知。在这里我们发现骨髓,血液和结肠C57中性粒细胞表达CD11bHi,并到达感染的结肠腔,在那里进行生产性NETosis。相比之下,而骨髓中C3H中性粒细胞的数量增加,血,和结肠,它们仍然是CD11bLo,被困在粘膜下层,远离C.rodentium,在那里他们经历了有害的NETosis。感染CRi9的C3H小鼠中的CD11bLo中性粒细胞,其触发中性粒细胞化学引诱物的表达,到达定殖位点,导致宿主存活。UC患者嗜中性粒细胞也显示出降低水平的活化/分化标志物CD16/CXCR4。这些结果,这表明中性粒细胞功能障碍会导致结肠炎恶化,为未来的治疗前景提供洞察力。
Citrobacter rodentium models infection with enteropathogenic Escherichia coli and ulcerative colitis (UC). While C57BL/6 (C57) mice recover, C3H/HeN (C3H) mice succumb to infection, partially due to increased colonic neutrophil elastase activity, also seen in UC patients; however, the underlying cause was unknown. Here, we found that bone marrow, blood, and colonic C57 neutrophils expressed (CD)11bHi and reached the infected colonic lumen, where they underwent productive NETosis. In contrast, while the number of C3H neutrophils increased in the bone marrow, blood, and colon, they remained CD11bLo and got trapped in the submucosa, away from C. rodentium, where they underwent harmful NETosis. CD11bLo neutrophils in C3H mice infected with CRi9, which triggers expression of neutrophil chemoattractants, reached the colonization site, resulting in host survival. UC patient neutrophils also displayed decreased levels of the activation/differentiation markers CD16/CXCR4. These results, suggesting that neutrophil malfunction contributes to exacerbated colitis, provide insight for future therapeutic prospects.