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Published on: July 30, 2012
Zebrafish use conserved CLR and TLR signaling pathways to respond to fungal PAMPs in zymosan
Erin Glass1,2, Stephan L Robinson2,3, Emily E Rosowski1,2
1Department of Biological Sciences, Clemson University, Clemson, SC.
Abstract:
Pattern recognition receptors (PRRs) such as C-type lectin receptors (CLRs) and Toll-like receptors (TLRs) are used by hosts to recognize pathogen-associated molecular patterns (PAMPs) in microorganisms and to initiate innate immune responses. While PRRs exist across invertebrate and vertebrate species, the functional homology of many of these receptors is still unclear. In this study, we investigate the innate immune response of zebrafish larvae to zymosan, a β-glucan-containing particle derived from fungal cell walls. Macrophages and neutrophils robustly respond to zymosan and are required for zymosan-induced activation of the NF-κB transcription factor. Full activation of NF-κB in response to zymosan depends on Card9/Syk and Myd88, conserved CLR and TLR adaptor proteins, respectively. Two putative CLRs, Clec4c and Sclra, are both required for maximal sensing of zymosan and NF-κB activation. Altogether, we identify conserved PRRs and PRR signaling pathways in larval zebrafish that promote recognition of fungal PAMPs. These results inform modeling of human fungal infections in zebrafish and increase our knowledge of the evolution and conservation of PRR pathways in vertebrates.
Insights
Zebrafish larvae use conserved pattern recognition receptors (PRRs) and signaling pathways to detect fungal components. This study identifies key receptors and pathways involved in innate immunity against fungal PAMPs.
Area of Science:
- Immunology
- Infectious Disease
- Developmental Biology
Background:
- Pattern recognition receptors (PRRs), including C-type lectin receptors (CLRs) and Toll-like receptors (TLRs), are crucial for host defense against pathogens.
- Understanding the functional homology of PRRs across species is essential for deciphering innate immunity.
- Zebrafish serve as a valuable vertebrate model for studying conserved immune mechanisms.
Purpose of the Study:
- To investigate the innate immune response of zebrafish larvae to zymosan, a fungal cell wall component.
- To identify conserved pattern recognition receptors and signaling pathways involved in fungal PAMP recognition in zebrafish.
- To establish zebrafish as a model for studying human fungal infections.
Main Methods:
- Exposure of zebrafish larvae to zymosan.
- Analysis of macrophage and neutrophil responses.
- Assessment of NF-κB transcription factor activation.
- Genetic analysis involving Card9/Syk, Myd88, Clec4c, and Sclra.
Main Results:
- Macrophages and neutrophils exhibit robust responses to zymosan.
- NF-κB activation by zymosan is dependent on Card9/Syk and Myd88 signaling pathways.
- Two CLRs, Clec4c and Sclra, are essential for maximal zymosan sensing and NF-κB activation.
- Conserved PRRs and signaling pathways for fungal PAMP recognition were identified in zebrafish.
Conclusions:
- Zebrafish larvae possess conserved innate immune mechanisms for recognizing fungal PAMPs.
- The identified PRRs and pathways are homologous to those found in other vertebrates.
- These findings support the use of zebrafish for modeling human fungal infections and studying immune evolution.
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