Spectrum of Trained Innate Immunity Induced by Low-Virulence Candida Species against Lethal Polymicrobial Intra-abdominal Infection
Open Access
- 1 August 2019
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 87 (8)
- https://doi.org/10.1128/iai.00348-19
Abstract
Polymicrobial intra-abdominal infections (IAI) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of polymicrobial IAI and demonstrated that coinfection with Candida albicans and Staphylococcus aureus (C. albicans/S. aureus) results in 80 to 90% mortality in 48 to 72 h due to robust local and systemic inflammation. Surprisingly, inoculation with Candida dubliniensis and S. aureus resulted in minimal mortality, and rechallenge of mice with lethal C. albicans/S. aureus conferred >90% protection up to 60 days postinoculation. Protection was mediated by Gr-1+ polymorphonuclear leukocytes, indicating a novel form of trained innate immunity (TII). The purpose of this study was to determine the microbial requirements and spectrum of innate-mediated protection. In addition to Candida dubliniensis, several other low-virulence Candida species (C. glabrata, C. auris, and C. albicans efg1Δ/Δ cph1Δ/Δ) and Saccharomyces cerevisiae conferred significant protection with or without S. aureus. For C. dubliniensis-mediated protection, hyphal formation was not required, with protection conferred as early as 7 days after primary challenge but not at 120 days, and also following multiple lethal C. albicans/S. aureus rechallenges. This protection also extended to a lethal intravenous (i.v.) C. albicans challenge but had no effect in the C. albicans vaginitis model. Finally, studies revealed the ability of the low-virulence Candida species that conferred protection to invade the bone marrow by 24 h post-primary challenge, with a positive correlation between femoral bone marrow fungal infiltration at 48 h and protection upon rechallenge. These results support and further extend the characterization of this novel TII in protection against lethal fungal-bacterial IAI and sepsis.Keywords
Funding Information
- HHS | NIH | National Institute of Allergy and Infectious Diseases (R01AI116025)
This publication has 55 references indexed in Scilit:
- Candida albicans-Staphylococcus aureus Polymicrobial Peritonitis Modulates Host Innate ImmunityInfection and Immunity, 2013
- Candida albicanspathogenicity mechanismsVirulence, 2013
- Mouse model of oropharyngeal candidiasisNature Protocols, 2012
- Polymicrobial Interactions: Impact on Pathogenesis and Human DiseaseClinical Microbiology Reviews, 2012
- Candida albicans Induces Selective Development of Macrophages and Monocyte Derived Dendritic Cells by a TLR2 Dependent SignallingPLOS ONE, 2011
- A Method for Generation of Bone Marrow-Derived Macrophages from Cryopreserved Mouse Bone Marrow CellsPLOS ONE, 2010
- Microbial interactions and differential protein expression inStaphylococcus aureus–Candida albicansdual-species biofilmsFEMS Immunology & Medical Microbiology, 2010
- The Compensatory Anti-inflammatory Response Syndrome (CARS) in Critically Ill PatientsClinics in Chest Medicine, 2008
- Evaluation of the Effects of Laparotomy and Laparoscopy on the Immune System in Intra-Abdominal Sepsis—A ReviewJournal of Investigative Surgery, 2008
- MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsisThe Journal of Experimental Medicine, 2007