Functional crosstalk across IMD and Toll pathways: insight into the evolution of incomplete immune cascades

Abstract

In insects, antimicrobial humoral immunity is governed by two distinct gene cascades, IMD pathway mainly targeting Gram-negative bacteria and Toll pathway preferentially targeting Gram-positive bacteria, which are widely conserved among diverse metazoans. However, recent genomic studies uncovered that IMD pathway is exceptionally absent in some hemipteran lineages like aphids and assassin bugs. How the apparently incomplete immune pathways have evolved with functionality is of interest. Here we report the discovery that, in the hemipteran stinkbug Plautia stali , both IMD and Toll pathways are present but their functional differentiation is blurred. Injection of Gram-negative bacteria and Gram-positive bacteria upregulated effector genes of both pathways. Notably, RNAi experiments unveiled significant functional permeation and crosstalk between IMD and Toll pathways: RNAi of IMD pathway genes suppressed upregulation of effector molecules of both pathways, where the suppression was more remarkable for IMD effectors; and RNAi of Toll pathway genes reduced upregulation of effector molecules of both pathways, where the suppression was more conspicuous for Toll effectors. These results suggest the possibility that, in hemipterans and other arthropods, IMD and Toll pathways are intertwined to target wider and overlapping arrays of microbes, which might have predisposed and facilitated the evolution of incomplete immune pathways.

Brown marmorated stink bug, Halyomorpha halys (Stål), genome: putative underpinnings of polyphagy, insecticide resistance potential and biology of a top worldwide pest

“…The lack of IMD is not necessarily unusual, as it has also not been found in the pea aphid, A. pisum; the body louse, Pediculus humanus corporis; or the deer tick, Ixodes scapularis. Indeed, recent evidence suggests IMD is absent among hempiterans [116,117], although its absence indicates an as-yet-uncharacterized means for transducing a PGRPinitiated signal in response to bacterial challenge.…”

Genome-enabled insights into the biology of thrips as crop pests

“…In Oncopeltus , IMD could not be identified by homology searches, but was identified by cloning the gene using degenerate primers [33]. IMD was also reported missing from the bedbug C. lectularius [30], but was later found using the Plautia stali IMD sequence as a query [100]. These findings in hemipterans illustrate that IMD sequences can be highly divergent and conclusions about their absence should be drawn with care.…”

“…In Tenebrio molitor , PGRP-SA recognizes both Gram positive and Gram negative bacteria [104]. Extensive cross reactivity of the Toll and IMD signaling pathway is the currently emerging picture from studies on other insects [100, 105, 106] and might have set the stage for multiple independent IMD losses in evolution [100].…”

A transcriptomic and proteomic atlas of expression in the Nezara viridula (Heteroptera: Pentatomidae) midgut suggests the compartmentalization of xenobiotic metabolism and nutrient digestion

“…For the phylogenomic analysis we first mapped the above-mentioned N. viridula unigenes onto the ortholog groups of OrthoDB v9 [23], at the Arthropoda node. Additionally, we downloaded and processed the transcriptomes of another three stink bugs so that we only keep one isoform per gene; the brown-winged green stink bug Plautia stali [45], Chalcocoris rutilans [46], and the green stink bug A. hilare [46]. These processed transcriptomes were then mapped on OrthoDB.…”