Impaired neutrophil migration underpins host susceptibility to infectious colitis

IF 7.9 2区 医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-10-01 DOI:10.1016/j.mucimm.2024.06.008
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Abstract

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.

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中性粒细胞迁移障碍是宿主易患传染性结肠炎的基础。
枸橼酸杆菌(Citrobacter rodentium)是感染肠致病性大肠杆菌和溃疡性结肠炎(UC)的模型。C57BL/6(C57)小鼠可恢复健康,而C3H/HeN(C3H)小鼠则会因感染而死亡,部分原因是结肠中性粒细胞弹性蛋白酶活性增加,这在溃疡性结肠炎患者中也可见到;然而,其根本原因尚不清楚。在这里,我们发现骨髓、血液和结肠中的 C57 中性粒细胞表达 CD11bHi,并到达受感染的结肠腔,在那里进行生产性 NETosis。与此相反,虽然骨髓、血液和结肠中的 C3H 中性粒细胞数量增加,但它们仍然是 CD11bLo 中性粒细胞,并被困在粘膜下层,远离鼠疫杆菌,并在那里发生有害的 NETosis。C3H小鼠感染CRi9后,CD11bLo中性粒细胞会触发中性粒细胞趋化因子的表达,从而到达定植部位,导致宿主存活。UC 患者中性粒细胞的活化/分化标志物 CD16/CXCR4 水平也有所下降。这些结果表明,中性粒细胞功能失调导致结肠炎恶化,为未来的治疗前景提供了启示。
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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