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

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.

• Publication year

  2024

• Venue

  Infection and Immunity

• Publication date

  2024-11-13

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1128/iai.00438-24PMID 39535200PMCID PMC11629626
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Microbiota signatures associated with invasive Candida albicans infection in the gastrointestinal tract of immunodeficient mice

  2024cited by this paper
• Profiling inflammatory outcomes of Candida albicans colonization and food allergy induction in the murine glandular stomach

  2024cited by this paper
• Interleukin inhibitors and the associated risk of candidiasis

  2024cited by this paper
• Opposing Effects of Interleukin-36γ and Interleukin-38 on Trained Immunity

  2023cited by this paper
• Candida Infection Associated with Anti-IL-17 Medication: A Systematic Analysis and Review of the Literature

  2022cited by this paper
• GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA.

  2022cited by this paper
• GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA.

  2022cited by this paper
• Contribution of the Microbiome, Environment, and Genetics to Mucosal Type 2 Immunity and Anaphylaxis in a Murine Food Allergy Model

  2022influential reference
• Interplay between Candida albicans and Lactic Acid Bacteria in the Gastrointestinal Tract: Impact on Colonization Resistance, Microbial Carriage, Opportunistic Infection, and Host Immunity

  2021cited by this paper
• Candida albicans Isolates 529L and CHN1 Exhibit Stable Colonization of the Murine Gastrointestinal Tract

  2021cited by this paper
• Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis

  2021cited by this paper
• Candida albicans Colonizes and Disseminates to the Gastrointestinal Tract in the Presence of the Microbiota in a Severe Combined Immunodeficient Mouse Model

  2021cited by this paper
• Nod2-deficient CD4+ T cells protect against Candida albicans infection

  2021cited by this paper
• Risk of candidiasis associated with interleukin-17 inhibitors: A real-world observational study of multiple independent sources

  2021cited by this paper
• GPR35 in Intestinal Diseases: From Risk Gene to Function

  2021cited by this paper
• Candida colonization of the esophagus and gastric mucosa; a comparison of patients taking proton pump inhibitors and those taking histamine receptor antagonist drugs

  2021cited by this paper
• Bile Acid Regulates the Colonization and Dissemination of Candida albicans from the Gastrointestinal Tract by Controlling Host Defense System and Microbiota

  2021cited by this paper
• The cross-kingdom interaction between Helicobacter pylori and Candida albicans

  2021cited by this paper
• Candida albicans Pma1p Contributes to Growth, pH Homeostasis, and Hyphal Formation

  2019cited by this paper
• Mast Cells Respond to Candida albicans Infections and Modulate Macrophages Phagocytosis of the Fungus

  2018cited by this paper
• Nod2 Deficiency in mice is Associated with Microbiota Variation Favouring the Expansion of mucosal CD4+ LAP+ Regulatory Cells

  2018cited by this paper
• IL-9 and Mast Cells Are Key Players of Candida albicans Commensalism and Pathogenesis in the Gut

  2018cited by this paper
• Candida is a protractive factor of chronic oral ulcers among usual outpatients

  2018cited by this paper
• A time-resolved multi-omic atlas of the developing mouse stomach

  2018cited by this paper
• The Bile Acid Receptor GPBAR1 Regulates the M1/M2 Phenotype of Intestinal Macrophages and Activation of GPBAR1 Rescues Mice from Murine Colitis

  2017cited by this paper
• Esophagitis and its causes: Who is “guilty” when acid is found “not guilty”?

  2017cited by this paper
• The gut mycobiome of the Human Microbiome Project healthy cohort

  2017cited by this paper
• How informative is the mouse for human gut microbiota research?

  2015cited by this paper
• Pathogenic NLRP3 Inflammasome Activity during Candida Infection Is Negatively Regulated by IL-22 via Activation of NLRC4 and IL-1Ra.

  2015cited by this paper
• The emerging world of the fungal microbiome.

  2013cited by this paper
• Modulation of Post-Antibiotic Bacterial Community Reassembly and Host Response by Candida albicans

  2013cited by this paper
• Development of a Dual-Index Sequencing Strategy and Curation Pipeline for Analyzing Amplicon Sequence Data on the MiSeq Illumina Sequencing Platform

  2013cited by this paper
• Fungi of the Murine Gut: Episodic Variation and Proliferation during Antibiotic Treatment

  2013cited by this paper
• Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

  2012cited by this paper
• Dectin-1 Is Not Required for Controlling Candida albicans Colonization of the Gastrointestinal Tract

  2012cited by this paper
• Sensing of mammalian IL-17A regulates fungal adaptation and virulence

  2012cited by this paper
• Candida albicans and Bacterial Microbiota Interactions in the Cecum during Recolonization following Broad-Spectrum Antibiotic Therapy

  2012cited by this paper
• Farnesoid X receptor protects human and murine gastric epithelial cells against inflammation-induced damage.

  2011cited by this paper
• Interplay between the Gastric Bacterial Microbiota and Candida albicans during Postantibiotic Recolonization and Gastritis

  2011influential reference
• The Bile Acid Receptor GPBAR-1 (TGR5) Modulates Integrity of Intestinal Barrier and Immune Response to Experimental Colitis

  2011cited by this paper
• Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system

  2010cited by this paper
• IL-22 defines a novel immune pathway of antifungal resistance

  2010cited by this paper
• The Bile Acid Receptor FXR Is a Modulator of Intestinal Innate Immunity1

  2009cited by this paper
• Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans

  2009cited by this paper
• Balancing inflammation and tolerance in vivo through dendritic cells by the commensal Candida albicans

  2009cited by this paper
• Lack of Toll IL-1R8 Exacerbates Th17 Cell Responses in Fungal Infection1

  2008cited by this paper
• IL‐23 and the Th17 pathway promote inflammation and impair antifungal immune resistance

  2007cited by this paper
• Functional yet Balanced Reactivity to Candida albicans Requires TRIF, MyD88, and IDO-Dependent Inhibition of Rorc1

  2007cited by this paper
• Gastric colonization of Candida albicans differs in mice fed commercial and purified diets.

  2005cited by this paper
• Adaptation of Candida albicans to the host environment: the role of morphogenesis in virulence and survival in mammalian hosts.

  2003cited by this paper
• CCL28 Has Dual Roles in Mucosal Immunity as a Chemokine with Broad-Spectrum Antimicrobial Activity 1

  2003cited by this paper
• Proinflammatory Activities of S100: Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion 1

  2003cited by this paper
• B7/CD28-Dependent CD4+CD25+ Regulatory T Cells Are Essential Components of the Memory-Protective Immunity to Candida albicans1

  2002cited by this paper
• Defective antifungal T-helper 1 (TH1) immunity in a murine model of allogeneic T-cell-depleted bone marrow transplantation and its restoration by treatment with TH2 cytokine antagonists.

  2001cited by this paper
• Dendritic Cells Discriminate between Yeasts and Hyphae of the Fungus Candida albicans

  2000cited by this paper
• Immunity to Candida albicans: Th1, Th2 cells and beyond.

  1999cited by this paper
• Neutrophils and the adaptive immune response to Candida albicans.

  1996cited by this paper
• T helper cell type 1 (Th1)- and Th2-like responses are present in mice with gastric candidiasis but protective immunity is associated with Th1 development.

  1995cited by this paper
• Mucosal and disseminated candidiasis in gnotobiotic SCID mice.

  1993cited by this paper
• Mucosal and systemic T helper cell function after intragastric colonization of adult mice with Candida albicans.

  1993cited by this paper
• Comparative morphology of the stomach of some laboratory mammals

  1989cited by this paper
• Candidal infection of gastric ulcers. Histology, incidence, and clinical significance.

  1979cited by this paper
• Effect of oral tetracycline, the microbial flora, and the athymic state on gastrointestinal colonization and infection of BALB/c mice with Candida albicans

  1979cited by this paper
• Microbial Interference Between Indigenous Yeast and Lactobacilli in the Rodent Stomach

  1969cited by this paper
• Localization of Indigenous Yeast in the Murine Stomach

  1967cited by this paper
• Growth and invasiveness of Candida albicans in the germ-free and conventional mouse after oral challenge.

  1966cited by this paper

• No citing papers are available for this paper.