Open AccessImmune mediation of HMG-like DSP1 via Toll-Spätzle pathway and its specific inhibition by salicylic acid analogs
Author(s) -
Md. Mahi Imam Mollah,
Shabbir Ahmed,
Yonggyun Kim
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009467
Subject(s) - spodoptera , biology , damp , immune system , pattern recognition receptor , microbiology and biotechnology , toll like receptor , biochemistry , signal transduction , receptor , innate immune system , immunology , gene , physics , meteorology , recombinant dna
Xenorhabdus hominickii , an entomopathogenic bacterium, inhibits eicosanoid biosynthesis of target insects to suppress their immune responses by inhibiting phospholipase A 2 (PLA 2 ) through binding to a damage-associated molecular pattern (DAMP) molecule called dorsal switch protein 1 (DSP1) from Spodoptera exigua , a lepidopteran insect. However, the signalling pathway between DSP1 and PLA 2 remains unknown. The objective of this study was to determine whether DSP1 could activate Toll immune signalling pathway to activate PLA 2 activation and whether X . hominickii metabolites could inhibit DSP1 to shutdown eicosanoid biosynthesis. Toll-Spätzle (Spz) signalling pathway includes two Spz ( SeSpz1 and SeSpz2 ) and 10 Toll receptors ( SeToll1-10 ) in S . exigua . Loss-of-function approach using RNA interference showed that SeSpz1 and SeToll9 played crucial roles in connecting DSP1 mediation to activate PLA 2 . Furthermore, a deletion mutant against SeToll9 using CRISPR/Cas9 abolished DSP1 mediation and induced significant immunosuppression. Organic extracts of X . hominickii culture broth could bind to DSP1 at a low micromolar range. Subsequent sequential fractionations along with binding assays led to the identification of seven potent compounds including 3-ethoxy-4-methoxyphenol (EMP). EMP could bind to DSP1 and prevent its translocation to plasma in response to bacterial challenge and suppress the up-regulation of PLA 2 activity. These results suggest that X . hominickii inhibits DSP1 and prevents its DAMP role in activating Toll immune signalling pathway including PLA 2 activation, leading to significant immunosuppression of target insects.