Zebrafish use conserved CLR and TLR signaling pathways to respond to fungal PAMPs in zymosan.
Erin GlassStephan L RobinsonEmily E RosowskiPublished in: bioRxiv : the preprint server for biology (2024)
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.
Keyphrases
- immune response
- signaling pathway
- transcription factor
- toll like receptor
- pi k akt
- nuclear factor
- lps induced
- dendritic cells
- cell wall
- inflammatory response
- endothelial cells
- oxidative stress
- induced apoptosis
- epithelial mesenchymal transition
- healthcare
- single cell
- stem cells
- blood pressure
- high glucose
- candida albicans
- cell therapy
- heart rate
- endoplasmic reticulum stress
- high intensity