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

Autor:	Zeise KD; Department of Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan, USA.; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Michigan, USA.; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA., Falkowski NR; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Michigan, USA.; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.; Division of Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA., Metcalf JD; Division of Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA., Brown CA; Division of Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA.; Advanced Research Computing, Information and Technology Services, University of Michigan, Ann Arbor, Michigan, USA., Huffnagle GB; Department of Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan, USA.; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Michigan, USA.; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.; Division of Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2024 Dec 10; Vol. 92 (12), pp. e0043824. Date of Electronic Publication: 2024 Nov 13.
DOI:	10.1128/iai.00438-24
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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