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. 2019 Jul 30;10:1785. doi: 10.3389/fimmu.2019.01785

Figure 2.

Figure 2

Comparison of Toll and TLR pathways from shrimp (A), Drosophila (B), and Human (C). Homologies between signaling components are depicted by similar shapes and colors. In shrimp, there are two extracellular-signaling routes leading to Toll pathway activation. Considering that many Spätzle (Spz) genes from shrimp have been identified and are able to induce Toll-Dorsal-controlled AMPs, the extracellular cleavage of Spz mediated by protease cascades could be similar to those of Drosophila. In the immune responses to microbial recognition, the protease cascades lead to the activation of Spz-processing enzymes (SPEs) to cleave full length Spz. Upon proteolytical processing, the Spz prodomain is cleaved, exposing the C-terminal Spz parts that are critical for binding of Toll. Spz binding to the Toll receptor initiates intracellular signaling. In contrast, shrimp Tolls are able to sense and directly bind to some conserved motifs, such as PGN, LPS, and ODN, from microbes, which are similar to those of Human. Upon binding to these motifs, shrimp Tolls are activated and initiate intracellular signaling. In the intracellular-signaling event, signaling cascades of shrimp Toll pathways broadly resemble those of Drosophila. After Toll activation, the adaptor MyD88 builds a signaling complex with Tube and Pelle. The MyD88-Tube-Pelle complex in turn recruits other regulators, such as Pellino and TRAF6, which leads to the phosphorylation and degradation of Cactus and thereby releases Dorsal (and/or Dif in Drosophila) to translocate to the nucleus and activate transcription. In Human, there are MyD88-dependent and MyD88-independent signal-transduction events. The intracellular signaling of Human can lead to active NF-κB, AP-1 and IFN regulatory factor 3/7 (IRF3/7) for their nuclear translocation and subsequent transcriptional activation of target genes. Of note, Toll3 from L. vannamei and Toll2 from P. clarkii have been shown to activate IRF and ATF4, respectively, leading to transcriptional synthesis of some antiviral effectors, such as Vago4/5 and ALFs.