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

<i>Candida albicans</i> 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, <i>C. albicans</i> induces gastritis without concurrent intestinal inflammation, suggesting that the stomach is particularly prone to fungal infection. We previously showed that <i>C. albicans</i> 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 <i>C. albicans</i> specifically in the limiting ridge have not been investigated. Here, we found that gastric dysbiosis was associated with <i>C. albicans</i> limiting ridge colonization and gastritis. We isolated the limiting ridge and evaluated the expression of over 90 genes involved in mucosal responses. <i>C. albicans</i> infection triggered a type 3 immune response marked by elevated <i>Il17a</i>, <i>Il17f</i>, <i>Il1b</i>, <i>Tnf</i>, and <i>Il36g</i>, as well as an upregulation of <i>Il12a</i>, <i>Il4</i>, <i>Il10</i>, and <i>l13</i>. Chemokine gene induction (including <i>Ccl2</i>, <i>Ccl3</i>, <i>Ccl4</i>, <i>Ccl1l</i>, <i>Cxcl1</i>, <i>Cxcl2</i>, <i>Cxcl9</i>, and <i>Cxcl10</i>) 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.