Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-κB signal transduction, and development.

Autor:	Brennan JJ; Department of Biology, Boston University, Boston, MA 02115., Messerschmidt JL; Department of Biology, Boston University, Boston, MA 02115., Williams LM; Department of Biology, Boston University, Boston, MA 02115., Matthews BJ; Department of Biology, Boston University, Boston, MA 02115., Reynoso M; Department of Biology, Boston University, Boston, MA 02115., Gilmore TD; Department of Biology, Boston University, Boston, MA 02115 gilmore@bu.edu.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Nov 21; Vol. 114 (47), pp. E10122-E10131. Date of Electronic Publication: 2017 Nov 06.
DOI:	10.1073/pnas.1711530114
Abstrakt:	In organisms from insects to vertebrates, Toll-like receptors (TLRs) are primary pathogen detectors that activate downstream pathways, specifically those that direct expression of innate immune effector genes. TLRs also have roles in development in many species. The sea anemone Nematostella vectensis is a useful cnidarian model to study the origins of TLR signaling because its genome encodes a single TLR and homologs of many downstream signaling components, including the NF-κB pathway. We have characterized the single N. vectensis TLR (Nv-TLR) and demonstrated that it can activate canonical NF-κB signaling in human cells. Furthermore, we show that the intracellular Toll/IL-1 receptor (TIR) domain of Nv-TLR can interact with the human TLR adapter proteins MAL and MYD88. We demonstrate that the coral pathogen Vibrio coralliilyticus causes a rapidly lethal disease in N. vectensis and that heat-inactivated V. coralliilyticus and bacterial flagellin can activate a reconstituted Nv-TLR-to-NF-κB pathway in human cells. By immunostaining of anemones, we show that Nv-TLR is expressed in a subset of cnidocytes and that many of these Nv-TLR-expressing cells also express Nv-NF-κB. Additionally, the nematosome, which is a Nematostella -specific multicellular structure, expresses Nv-TLR and many innate immune pathway homologs and can engulf V. coralliilyticus Morpholino knockdown indicates that Nv-TLR also has an essential role during early embryonic development. Our characterization of this primitive TLR and identification of a bacterial pathogen for N. vectensis reveal ancient TLR functions and provide a model for studying the molecular basis of cnidarian disease and immunity. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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