These results suggest that in T. castaneum single microbes may activate concomitantly both Toll and IMD pathways; the AMP genes are likely to be regulated in
the context of respective degrees of dependence on either the Toll or IMD pathways rather than by elicitor classes. Thus, more promiscuous activation and usage of the two pathways are likely to occur in T. castaneum through signaling crosstalk, and the independence of the two pathways seems to be weaker than in Drosophila. We consider that there are at least three distinct levels where signaling crosstalk could occur, Trametinib mw sensor proteins, intracellular signaling components and transcription factors/response elements. T. castaneum and D. melanogaster have different numbers
of PGRPs. T. castaneum has seven PGRP proteins while D. melanogaster has 13 PGRP proteins [6] and [39]. A smaller number of PGRP proteins suggests T. castaneum PGRPs have more multiple functions (e.g. broader or less-stringent specificity of PG binding) than in D. melanogaster whereas promiscuous PG binding in vitro was also reported for Drosophila PGRP-SA and PGRP-LC variants [44]. Another beetle species T. moliter seems to have a somewhat different microbe sensing system from D. melanogaster [33]. T. moliter PGRP-SA can recognize both gram-positive and gram-negative bacteria, and selleck compound can activate the serine protease cascade leading to the cleavage of Späzle, whereas the T. moliter IMD pathway is not clearly described to date. T. castaneum may have a similar promiscuous sensing system. One or more T. castaneum PGRPs possibly sense Ec, Ml and Sc as a single or complexed form and activate both the Toll and IMD pathways. Crosstalk between the two signaling ADAM7 pathways may occur at the level of intracellular signaling. One of the candidate components in the intracellular pathways is FADD, an
adapter protein functioning between IMD and Dredd. In Drosophila, biochemical studies have revealed that FADD can interact with IMD, Dredd and MyD88 [45] and [46]. Similarly, the crosstalk mediated by FADD may occur more strongly in T. castaneum than in D. melanogaster. Crosstalk through heterodimerization of NF-κB molecules at the terminal ends of the two signaling pathways, may also occur. In D. melanogaster, these transcription factors form dimers and translocate to the nucleus when activated. Genetic studies have revealed that DIF/Dosal is activated mainly by the Toll pathway [23] and [47], and that Relish is activated mainly by the IMD pathway [32]. However, for example, a subsequent study revealed that the induction of CecropinA1 by Ml requires Relish, and that induction of AMP genes by different types of fungi requires Dif or Relish while these authors also suggested signal crosstalk at different levels [48]. A recent study demonstrated that NF-κB heterodimers (e.g.