The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo
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In vitro studies have indicated the importance of Toll-like receptor (TLR) signaling in response to the fungal pathogens Candida albicans and Aspergillus fumigatus. However, the functional consequences of the complex interplay between fungal morphogenesis and TLR signaling in vivo remain largely undefined. In this study we evaluate the impact of the IL-1R/TLR/myeloid differentiation primary response gene 88 (MyD88)-dependent signaling pathway on the innate and adaptive Th immunities to C. albicans and A. fumigatus in vivo. It was found that 1) the MyD88-dependent pathway is required for resistance to both fungi; 2) the involvement of the MyD88 adapter may occur through signaling by distinct members of the IL-1R/TLR superfamily, including IL-1R, TLR2, TLR4, and TLR9, with the proportional role of the individual receptors varying depending on fungal species, fungal morphotypes, and route of infection; 3) individual TLRs and IL-1R activate specialized antifungal effector functions on neutrophils, which correlates with susceptibility to infection; and 4) MyD88-dependent signaling on dendritic cells is crucial for priming antifungal Th1 responses. Thus, the finding that the innate and adaptive immunities to C. albicans and A. fumigatus require the coordinated action of distinct members of the IL-1R/TLR superfamily acting through MyD88 makes TLR manipulation amenable to the induction of host resistance to fungi.
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IL-1R signaling is critical for neutrophil recruitment and function and plays an important role in host defense against C. albicans in oral mucosa and systemic infection.
“IL-1R signaling is critical for neutrophil recruitment and function and plays an important role in the host defense against C. albicans in oral mucosa and systemic infection [31, 32]”
IL-1R signaling is critical for neutrophil function.
“IL-1R signaling is critical for neutrophil function [26, 31, 32]”
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- Authors
- Bellocchio, S., Montagnoli, C., Bozza, S., Gaziano, R., Rossi, G., Mambula, S. S., Vecchi, A., Mantovani, A., Levitz, S. M., & Romani, L.
- Affiliations
- University of Perugia (IT)
- Boston University (US)
- Mario Negri Institute for Pharmacological Research (IT)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-03-01
- Volume
- 172
- Issue
- 5
- Pages
- 3059-3069
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1519886765
- Cited by
- 515
- References
- 1
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 9 · 2023: 3 · 2022: 11 · 2021: 12 · 2020: 13 · 2019: 17 · 2018: 18 · 2017: 21 · 2016: 18 · 2015: 15 · 2014: 36 · 2013: 21 · 2012: 31
- FWCI
- 14.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI37532, R01AI025780, R01AI037532, AI-25780)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- Toll-like receptors, MyD88 signaling, fungal infection, Candida albicans, Aspergillus fumigatus, innate immunity, adaptive immunity, Th1 response, dendritic cells, neutrophils, fungal morphogenesis
- MeSH terms
- Animals, Antifungal Agents, Antigens, Differentiation, Aspergillosis, Aspergillus fumigatus, Candida albicans, Candidiasis, Female, T-Lymphocytes, Helper-Inducer, Immunity, Cellular, Immunity, Innate, Membrane Glycoproteins, Mice, Inbred C57BL, Neutrophils, Receptors, Cell Surface, Receptors, Immunologic, Tumor Necrosis Factor-alpha, Signal Transduction, Receptors, Interleukin-1, Mice, Knockout, Genetic Predisposition to Disease, Adaptor Proteins, Signal Transducing, Toll-Like Receptors, Toll-Like Receptor 2, Toll-Like Receptor 4, Mice, Myeloid Differentiation Factor 88
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