Silica crystals activate toll-like receptors and inflammasomes to promote local and systemic immune responses in zebrafish
- Tyrkalska, S.D., Pedoto, A., Martínez-López, A., Ros-Lucas, J.A., Mesa-Del-Castillo, P., Candel, S., Mulero, V.
- Developmental and comparative immunology 138: 104523 (Journal)
- Registered Authors
- Mulero, Victor
- Fibrosis, Inflammasome, Inflammation, Silica crystals, Silicosis, TLRs, Zebrafish
- MeSH Terms
- NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
- Silicon Dioxide/adverse effects
- Toll-Like Receptors/metabolism
- 36055417 Full text @ Dev. Comp. Immunol.
Tyrkalska, S.D., Pedoto, A., Martínez-López, A., Ros-Lucas, J.A., Mesa-Del-Castillo, P., Candel, S., Mulero, V. (2022) Silica crystals activate toll-like receptors and inflammasomes to promote local and systemic immune responses in zebrafish. Developmental and comparative immunology. 138:104523.
Silica crystals are potent activators of the inflammasome that cause a fibrotic lung disease, called silicosis, with no effective treatment available. We report here that injection of silica crystals into the hindbrain ventricle of zebrafish embryos led to the initiation of local and systemic immune responses driven through both TLR- and inflammasome-dependent signaling pathways, followed by induction of pro-fibrotic markers. Genetic and pharmacological analysis revealed that the Nlrp3 inflammasome regulated silica crystal-induced inflammation and pyroptotic cell death, but not emergency myelopoiesis. In addition, Cxcl8a/Cxcr2-dependent recruitment of myeloid cells to silica crystals was required to promote emergency myelopoiesis and systemic inflammation. The zebrafish model of silicosis developed here shed light onto the molecular mechanisms involved in the activation of the immune system by silica crystals.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes