Toll-Like Receptors, Associated Biological Roles, and Signaling Networks in Non-Mammals

Abstract

The innate immune system is the first line of defense against pathogens, which is initiated by the recognition of pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs). Among all the PRRs identified, the toll-like receptors (TLRs) are the most ancient class, with the most extensive spectrum of pathogen recognition. Since the first discovery of Toll in Drosophila melanogaster, numerous TLRs have been identified across a wide range of invertebrate and vertebrate species. It seems that TLRs, the signaling pathways that they initiate, or related adaptor proteins are essentially conserved in a wide variety of organisms, from Porifera to mammals. Molecular structure analysis indicates that most TLR homologs share similar domain patterns and that some vital participants of TLR signaling co-evolved with TLRs themselves. However, functional specification and emergence of new signaling pathways, as well as adaptors, did occur during evolution. In addition, ambiguities and gaps in knowledge still exist regarding the TLR network, especially in lower organisms. Hence, a systematic review from the comparative angle regarding this tremendous signaling system and the scenario of evolutionary pattern across Animalia is needed. In the current review, we present overview and possible evolutionary patterns of TLRs in non-mammals, hoping that this will provide clues for further investigations in this field.

A survey of TIR domain sequence and structure divergence

“…Like group 2, the largest group of plant TIR domains, group 3 represents a family of (germline) receptors that detect pathogens. Most group 3 proteins are from insects and vertebrates, though they are also present in lower protostomes and deuterostomes, but not in sponges or flatworms (Gauthier et al 2010;Nie et al 2018;Wiens et al 2007) (Supplemental Fig. 2)-suggesting group 3-specific features emerged during early evolution of metazoan body plans.…”

The how and why of lncRNA function: An innate immune perspective

“…These receptors couple pathogensensing to activation of downstream signaling cascades resulting in activation of numerous transcription factors, including NF-kappaB (NF-κB) and interferon regulatory factors (IRFs) that can act in combination to both positively and negatively regulate the expression of thousands of genes [36,37]. There are 10 different TLR genes in the human genome and 13 TLR genes in mice [38][39][40], each binding a different PAMP [41]. Using this extensively studied biological system, we identified the first example of a TLR-stimulated lncRNA, lincRNA-Cox2, which was capable of positively and negatively regulating distinct types of innate immune genes [42][43][44][45][46].…”

The round goby genome provides insights into mechanisms that may facilitate biological invasions

“…Most vertebrate genomes contain one to three members of each subfamily, with occasional species-specific small gene expansions. Examples are 4 copies of TLR14 in frog (Xenopus laevis), 3 copies of TLR5 in channel catfish (Ictalurus punctatus), or 2 copies of TLR2 in chicken (Gallus gallus) [96][97][98][99]. As expected for a teleost, the round goby genome does not contain the LPS-detecting TLR4 genes.…”