Mucosal damage and neutropenia are required for Candida albicans dissemination

Koh, Andrew Y; Köhler, Julia R; Coggshall, Kathleen T; Van Rooijen, Nico; Pier, Gerald B

doi:10.1371/journal.ppat.0040035

Cited by 360Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

Mucosal damage and neutropenia are required for Candida albicans dissemination

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Koh, Andrew Y, Köhler, Julia R, Coggshall, Kathleen T, Van Rooijen, Nico, Pier, Gerald B·2008·PLoS Pathogens

DOI 10.1371/journal.ppat.0040035PMC PMC2242836

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Abstract

Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI) colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for allowing widespread invasive C. albicans disease. We investigated these parameters in a mouse model of C. albicans GI colonization that led to systemic spread after administration of immunosuppression and mucosal damage. After depleting resident GI intestinal flora with antibiotic treatment and achieving stable GI colonization levels of C. albicans, it was determined that systemic chemotherapy with cyclophosphamide led to 100% mortality, whereas selective neutrophil depletion, macrophage depletion, lymphopenia or GI mucosal disruption alone resulted in no mortality. Selective neutrophil depletion combined with GI mucosal disruption led to disseminated fungal infection and 100% mortality ensued. GI translocation and dissemination by C. albicans was also dependent on the organism's ability to transform from the yeast to the hyphal form. This mouse model of GI colonization and fungemia is useful for studying factors of innate host immunity needed to prevent invasive C. albicans disease as well as identifying virulence factors that are necessary for fungal GI colonization and dissemination. The model may also prove valuable for evaluating therapies to control C. albicans infections.

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Neutrophils are crucial for fungal defense.
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Authors: Koh, A. Y., Köhler, J. R., Coggshall, K. T., Van Rooijen, N., & Pier, G. B.
Affiliations: Brigham and Women's Hospital (US)
Boston Children's Hospital (US)
Corresponding author: Koh, Andrew Y
ORCID: Koh, Andrew Y
Köhler, Julia R
Pier, Gerald B
Venue: PLoS Pathogens
Publisher: Public Library of Science (PLoS)
Published: 2008-02-15
Volume: 4
Issue: 2
Pages: e35
ISSN: 1553-7366 (ISSN-L)
1553-7374
DOI: 10.1371/journal.ppat.0040035
PMC: PMC2242836
OpenAlex: W2012600634
Cited by: 360
References: 65
Citations by year: 2026: 6 · 2025: 18 · 2024: 22 · 2023: 20 · 2022: 18 · 2021: 24 · 2020: 25 · 2019: 23 · 2018: 18 · 2017: 25 · 2016: 20 · 2015: 27 · 2014: 26 · 2013: 20 · 2012: 17
FWCI: 10.99
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS Pathogens (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
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Funders: National Institutes of Health
National Institute of Allergy and Infectious Diseases (R01AI022535, AI-22535, K08AI062983, AI62983, R21AI064715)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords: Candida albicans, fungemia, intestinal colonization, mucosal injury, neutropenia, neutrophil depletion, disseminated fungal infection, innate immunity, cyclophosphamide, chemotherapy-induced immunosuppression, hyphal morphogenesis, macrophage depletion, lymphopenia, cancer patients
MeSH terms: Animals, Anti-Bacterial Agents, Candida albicans, Candidiasis, Cyclophosphamide, Disease Models, Animal, Female, Immunosuppression Therapy, Longevity, Mice, Inbred C3H, Mucous Membrane, Neutropenia, Mice, Knockout, Bacterial Translocation, Gene Silencing, Gastrointestinal Tract, Mice

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Mucosal damage and neutropenia are required for Candida albicans dissemination

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