Gene expression profiling reveals host defense strategies for restricting Candida albicans invasion and gastritis to the limiting ridge of the murine stomach.

IF 2.9 3区 医学 Q3 IMMUNOLOGY Infection and Immunity Pub Date : 2024-11-13 DOI:10.1128/iai.00438-24
Karen D Zeise, Nicole R Falkowski, Joseph D Metcalf, Christopher A Brown, Gary B Huffnagle
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Abstract

Candida albicans is a fungal constituent of the human gastrointestinal microbiota that can tolerate acidic environments like the stomach, where it can be associated with ulcers and chronic gastritis. In mice, C. albicans induces gastritis without concurrent intestinal inflammation, suggesting that the stomach is particularly prone to fungal infection. We previously showed that C. albicans invasion in the limiting ridge does not extend to or elicit an inflammatory response in the adjacent glandular region, indicating regionalized gastritis in the murine stomach. However, the molecular pathways involved in the host response to C. albicans specifically in the limiting ridge have not been investigated. Here, we found that gastric dysbiosis was associated with C. albicans limiting ridge colonization and gastritis. We isolated the limiting ridge and evaluated the expression of over 90 genes involved in mucosal responses. C. albicans infection triggered a type 3 immune response marked by elevated Il17a, Il17f, Il1b, Tnf, and Il36g, as well as an upregulation of Il12a, Il4, Il10, and l13. Chemokine gene induction (including Ccl2, Ccl3, Ccl4, Ccl1l, Cxcl1, Cxcl2, Cxcl9, and Cxcl10) coincided with an influx of neutrophils, monocytes/macrophages, and eosinophils. Hyphal invasion caused tissue damage, epithelial remodeling, and upregulation of genes linked to epithelium signaling and antimicrobial responses in the limiting ridge. Our findings support a need for continued exploration into the interactions between the immunological milieu, the host microbiota, and clinical interventions such as the use of antibiotics and immunotherapeutic agents and their collective impact on invasive candidiasis risk.

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基因表达谱分析揭示了将白色念珠菌入侵和胃炎限制在小鼠胃边缘脊的宿主防御策略。
白色念珠菌是人类胃肠道微生物群中的一种真菌成分,它能耐受胃等酸性环境,在胃中可能与溃疡和慢性胃炎有关。在小鼠体内,白僵菌会诱发胃炎,但不会同时引起肠道炎症,这表明胃特别容易受到真菌感染。我们以前的研究表明,白僵菌侵入胃边缘脊并不会延伸到邻近的腺体区域,也不会引起腺体区域的炎症反应,这表明小鼠胃炎是区域性的。然而,尚未研究宿主对限制脊中的白细胞特异性反应所涉及的分子途径。在这里,我们发现胃内菌群失调与白僵菌限制脊定植和胃炎有关。我们分离了限制脊,并评估了涉及粘膜反应的 90 多个基因的表达。白僵菌感染引发了3型免疫反应,表现为Il17a、Il17f、Il1b、Tnf和Il36g的升高,以及Il12a、Il4、Il10和l13的上调。趋化因子基因诱导(包括 Ccl2、Ccl3、Ccl4、Ccl1l、Cxcl1、Cxcl2、Cxcl9 和 Cxcl10)与中性粒细胞、单核细胞/巨噬细胞和嗜酸性粒细胞的涌入同时发生。头孢菌素入侵会造成组织损伤、上皮重塑以及与上皮信号转导和限制脊中抗菌反应相关的基因上调。我们的研究结果表明,有必要继续探索免疫环境、宿主微生物群和临床干预(如使用抗生素和免疫治疗剂)之间的相互作用及其对侵袭性念珠菌病风险的共同影响。
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来源期刊
Infection and Immunity
Infection and Immunity 医学-传染病学
CiteScore
6.00
自引率
6.50%
发文量
268
审稿时长
3 months
期刊介绍: Infection and Immunity (IAI) provides new insights into the interactions between bacterial, fungal and parasitic pathogens and their hosts. Specific areas of interest include mechanisms of molecular pathogenesis, virulence factors, cellular microbiology, experimental models of infection, host resistance or susceptibility, and the generation of innate and adaptive immune responses. IAI also welcomes studies of the microbiome relating to host-pathogen interactions.
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