Impaired neutrophil migration underpins host susceptibility to infectious colitis.

Autor: Sanchez-Garrido J; Department of Life Sciences, Imperial College, London, United Kingdom. Electronic address: julia.sanchez-garrido08@imperial.ac.uk., Baghshomali YN; Department of Life Sciences, Imperial College, London, United Kingdom., Kaushal P; Functional Proteomics Group, Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom., Kozik Z; Functional Proteomics Group, Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom., Perry RW; Department of Metabolism, Digestion and Reproduction, Imperial College, London, United Kingdom., Williams HRT; Department of Metabolism, Digestion and Reproduction, Imperial College, London, United Kingdom., Choudhary J; Functional Proteomics Group, Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom., Frankel G; Department of Life Sciences, Imperial College, London, United Kingdom.
Jazyk: angličtina
Zdroj: Mucosal immunology [Mucosal Immunol] 2024 Oct; Vol. 17 (5), pp. 939-957. Date of Electronic Publication: 2024 Jun 25.
DOI: 10.1016/j.mucimm.2024.06.008
Abstrakt: 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)11b Hi 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 CD11b Lo and got trapped in the submucosa, away from C. rodentium, where they underwent harmful NETosis. CD11b Lo neutrophils in C3H mice infected with CR i9 , 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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