Evolution of CEACAM pathogen decoy receptors in primates.

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation Pub Date : 2024-12-01 DOI:10.1111/eci.14356

Wolfgang Zimmermann, Robert Kammerer

{"title":"Evolution of CEACAM pathogen decoy receptors in primates.","authors":"Wolfgang Zimmermann, Robert Kammerer","doi":"10.1111/eci.14356","DOIUrl":null,"url":null,"abstract":"Background: CEACAM1 in leukocytes controls cell activation during inflammation. This and its expression in epithelial cells led to frequent independent appropriation of CEACAM1 as receptor by pathogens in humans and other species to gain host access and to downregulate its immune response. As a countermeasure, decoy receptors with CEACAM1-like pathogen-binding domains evolved. The granulocyte-specific human CEACAM3 endocytic receptor diverts CEACAM1-binding pathogens to neutrophils for internalization and destruction. The role of the glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 which can also bind CEACAM1-targeting pathogens in humans is less clear.Methods: We analyzed the selection of CEACAMs to avoid pathogen binding and to maintain similarity between pathogen receptors and decoy receptors in 148 primate species.Results: Notably, functional CEACAM3 genes were not found in gibbons and New World monkeys. Interestingly, CEACAM6 in these primates exhibits similar high ratios of rates of nonsynonymous and synonymous substitution (dN/dS) in their pathogen-binding N domain exons as found for CEACAM1. High dN/dS ratios are indicative of selection for diversification typically seen in pathogen receptors. Human CEACAM6 is expressed on granulocytes and epithelial cells. Therefore, CEACAM6 could substitute for the missing endocytic receptor CEACAM3. In nearly all investigated primate groups also N exons of the epithelially expressed CEACAM5 exhibit selection for diversification. In African populations, five high-frequency polymorphisms are observed in the pathogen-binding region of CEACAM5 (I80V, V83A, I100T, I112V, I113T) with 3-4 polymorphisms combined in the same individual. These polymorphisms correspond to CEACAM1 pathogen-binding domain sequences.Conclusion: The glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 are under selection to maintain similarity to the pathogen receptor CEACAM1 in most primate species, indicating a function as decoy receptors.","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 Suppl 2 ","pages":"e14356"},"PeriodicalIF":4.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646289/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Clinical Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/eci.14356","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background: CEACAM1 in leukocytes controls cell activation during inflammation. This and its expression in epithelial cells led to frequent independent appropriation of CEACAM1 as receptor by pathogens in humans and other species to gain host access and to downregulate its immune response. As a countermeasure, decoy receptors with CEACAM1-like pathogen-binding domains evolved. The granulocyte-specific human CEACAM3 endocytic receptor diverts CEACAM1-binding pathogens to neutrophils for internalization and destruction. The role of the glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 which can also bind CEACAM1-targeting pathogens in humans is less clear.

Methods: We analyzed the selection of CEACAMs to avoid pathogen binding and to maintain similarity between pathogen receptors and decoy receptors in 148 primate species.

Results: Notably, functional CEACAM3 genes were not found in gibbons and New World monkeys. Interestingly, CEACAM6 in these primates exhibits similar high ratios of rates of nonsynonymous and synonymous substitution (dN/dS) in their pathogen-binding N domain exons as found for CEACAM1. High dN/dS ratios are indicative of selection for diversification typically seen in pathogen receptors. Human CEACAM6 is expressed on granulocytes and epithelial cells. Therefore, CEACAM6 could substitute for the missing endocytic receptor CEACAM3. In nearly all investigated primate groups also N exons of the epithelially expressed CEACAM5 exhibit selection for diversification. In African populations, five high-frequency polymorphisms are observed in the pathogen-binding region of CEACAM5 (I80V, V83A, I100T, I112V, I113T) with 3-4 polymorphisms combined in the same individual. These polymorphisms correspond to CEACAM1 pathogen-binding domain sequences.

Conclusion: The glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 are under selection to maintain similarity to the pathogen receptor CEACAM1 in most primate species, indicating a function as decoy receptors.

查看原文本刊更多论文

灵长类动物CEACAM病原体诱饵受体的进化。

背景：白细胞中的CEACAM1控制炎症期间的细胞活化。这一点及其在上皮细胞中的表达导致人类和其他物种的病原体经常独立占用CEACAM1作为受体，以获得宿主通路并下调其免疫反应。作为对策，具有ceacam1样病原体结合结构域的诱饵受体进化了。粒细胞特异性的人CEACAM3内吞受体将ceacam1结合的病原体转移到中性粒细胞中进行内化和破坏。糖基磷脂酰肌醇锚定的CEACAM5和CEACAM6在人类中也可以结合靶向ceacam1的病原体，其作用尚不清楚。方法：分析148种灵长类动物中CEACAMs的选择，以避免病原体结合，并保持病原体受体和诱饵受体之间的相似性。结果：值得注意的是，在长臂猿和新大陆猴中未发现功能性CEACAM3基因。有趣的是，在这些灵长类动物中，CEACAM6在其病原体结合的N域外显子中表现出与CEACAM1相似的高比率的非同义和同义替换（dN/dS）。较高的dN/dS比率表明了在病原体受体中常见的多样化选择。人CEACAM6在粒细胞和上皮细胞上表达。因此，CEACAM6可以替代缺失的内吞受体CEACAM3。在几乎所有研究的灵长类群体中，上皮表达的CEACAM5的N个外显子也表现出多样化的选择。在非洲人群中，CEACAM5的病原体结合区存在5种高频多态性（I80V, V83A, I100T, I112V, I113T），在同一个体中存在3-4个多态性。这些多态性对应于CEACAM1病原体结合域序列。结论：在大多数灵长类动物中，糖基磷脂酰肌醇锚定的CEACAM5和CEACAM6被选择以保持与病原体受体CEACAM1的相似性，表明它们具有诱骗受体的功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.