Abstract

Defensive systems against pathogens are responsible not only for survival or lifetime of an individual but also for the evolution of a species. Innate immunity is expected to be more important for invertebrates than mammals, given that adaptive immunity has not been acquired in the former. Toll-like receptors (TLRs) have been shown to play a crucial role in host defense of pathogenic microbes in innate immunity of mammals. Recent genome-wide analyses have suggested that TLR or their related genes are conserved in invertebrates. In particular, numerous TLR-related gene candidates were detected in deuterostome invertebrates, including a sea urchin (222 TLR-related gene candidates) and amphioxus (72 TLR-related gene candidates). Molecular phylogenetic analysis verified that most of sea urchin or amphioxus TLR candidates are paralogous, suggesting that these organisms expanded TLR-related genes in a species-specific manner. In contrast, another deuterostome invertebrate, the ascidian Ciona intestinalis, was found to possess only two TLR genes. Moreover, Ciona TLRs, Ci-TLR1 and Ci-TLR2, were shown to possess “hybrid” functionality of mammalian TLRs. Such functionality of Ci-TLRs could not be predicted by sequence comparison with vertebrate TLRs, indicating confounding evolutionary lineages of deuterostome invertebrate TLRs or their candidates. In this review article, we present recent advances in studies of TLRs or their candidates among deuterostome invertebrates, and provide insight into an evolutionary process of TLRs.

Highlights

  • Innate immunity is a primary defense system against invading pathogens in invertebrates, in which adaptive immune systems have not been fully developed

  • Most invertebrate immune systems diverged among species, whereas recent genome surveys of various organisms revealed that Toll-like receptors (TLRs) or their related proteins are essentially conserved in an extensive range of organisms from cnidarians to mammals

  • The number of TLRs in vertebrates does not dramatically differ among species; 10 for human and 12 for Takifugu (Roach et al, 2005; Matsuo et al, 2008). These findings suggest that molecular and functional studies of deuterostome invertebrate TLRs have led to their evolution and diversity as well as to the elucidation of molecular mechanisms underlying their innate immunity

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Summary

INTRODUCTION

Innate immunity is a primary defense system against invading pathogens in invertebrates, in which adaptive immune systems have not been fully developed. Deuterostome invertebrates and vertebrates conserve TLR-directed innate immunity (Akira and Takeda, 2004; Khalturin et al, 2004; Dunne and O’Neill, 2005; Iwanaga and Lee, 2005; Roach et al, 2005; Takeda and Akira, 2005; Ishii et al, 2007; Takano et al, 2007; Davidson et al, 2008; Fedders et al, 2008; Matsuo et al, 2008; Oshiumi et al, 2008; Rast and Messier-Solek, 2008; Bosch et al, 2009; Schikorski et al, 2009; Yu et al, 2009; Macagno et al, 2010; Satake and Sasaki, 2010; Cuvillier-Hot et al, 2011; Park et al, 2011; Wu et al, 2011) These studies suggest that the TLR system of immune receptors is the most widely distributed throughout the deuterostomes and reveal several characteristics of TLRs specific to deuterostome invertebrates. TLRs: CHARACTERIZATION, FAMILY MEMBERS, PATHOGEN RECOGNITION, AND SIGNAL TRANSDUCTION Toll-like receptors were characterized originally as a mammalian ortholog of the Drosophila melanogaster (fruitfly) transmembrane protein Toll, which is responsible for antifungal protection and www.frontiersin.org

Number of LRR
Plasma membrane Plasma membrane
CONCLUSIONS AND PERSPECTIVES
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