Abstract
An anuran amphibian, South African clawed frog (Xenopus laevis), is used to study the immune system, as it possesses a set of acquired immune system represented by T and B lymphocytes and the immunoglobulins. The acquired immune system is impaired throughout the larva and the metamorphosis stage in the amphibians. On the other hand, the role of innate immune system in the tadpole remains unclear. Recently, insect Toll protein homologues, namely, Toll-like receptors (TLRs), have been identified as sensors recognizing microbe-pattern molecules in vertebrates. Whole-genome analysis of Xenopus tropicalis supported the existence of the tlr genes in the frog. In this study, we annotated 20 frog tlr gene nucleotide sequences from the latest genome assembly version 4.1 on the basis of homology and identified cDNAs of the predicted frog TLR proteins. Phylogenetic analysis showed that the repertoire of the frog TLRs consisted of both fish- and mammalian-type TLRs. We showed that the frog TLRs are constitutively expressed in the tadpole as well as in the adult frog. Our results suggest that tadpoles are protected from microbes by the innate system that includes TLRs, despite impaired acquired immune system in tadpoles. This is the first report on the properties of TLRs in the most primitive terrestrial animals like amphibia.
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References
Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732–738
Belvin MP, Anderson KV (1996) A conserved signaling pathway: the Drosophila toll-dorsal pathway. Annu Rev Cell Dev Biol 12:393–416
da Silva Correia J, Soldau K, Christen U, Tobias PS, Ulevitch RJ (2001) Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. Transfer from CD14 to TLR4 and MD-2. J Biol Chem 276:21129–21135
Du Pasquier L, Schwager J, Flajnik MF (1989) The immune system of Xenopus. Annu Rev Immunol 7:251–75
Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408:740–745
Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3:196–200
Hirono I, Takami M, Miyata M, Miyazaki T, Han HJ, Takano T, Endo M, Aoki T (2004) Characterization of gene structure and expression of two toll-like receptors from Japanese flounder, Paralichthys olivaceus. Immunogenetics 56:38–46
Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S (1999) Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 162:3749–3752
Ishii A, Matsuo A, Sawa H, Tsujita T, Shida K, Matsumoto M, Seya T (2007) Lamprey Toll-like receptors with properties distinct from those of the variable lymphocyte receptors. J Immunol 178(1):397–406
Janeway CA Jr (1989) Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 54 Pt 1:1–13
Jiang Q, Akashi S, Miyake K, Petty HR (2000) Lipopolysaccharide induces physical proximity between CD14 and toll-like receptor 4 (TLR4) prior to nuclear translocation of NF-kappa B. J Immunol 165:3541–3544
Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86:973–983
Marchalonis JJ, Schluter SF, Bernstein RM, Hohman VS (1998) Antibodies of sharks: revolution and evolution. Immunol Rev 166:103–22
Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–45
Medzhitov R, Preston-Hurlburt P, Janeway, CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394–397
Nagai Y, Akashi S, Nagafuku M, Ogata M, Iwakura Y, Akira S, Kitamura T, Kosugi A, Kimoto M, Miyake K (2002) Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol 3:667–672
Oshiumi H, Tsujita T, Shida K, Matsumoto M, Ikeo K, Seya T (2003) Prediction of the prototype of the human Toll-like receptor gene family from the pufferfish, Fugu rubripes, genome. Immunogenetics 54:791–800
Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L, Aderem A (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA 97:13766–13771
Pancer Z, Cooper MD (2006) The evolution of adaptive immunity. Annu Rev Immunol 24:497–518
Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088
Pujol N, Link EM, Liu LX, Kurz CL, Alloing G, Tan MW, Ray KP, Solari R, Johnson CD, Ewbank JJ (2001) A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans. Curr Biol 11:809–821
Roach JC, Glusman G, Rowen L, Kaur A, Purcell MK, Smith KD, Hood LE, Aderem A (2005) The evolution of vertebrate Toll-like receptors. Proc Natl Acad Sci USA 102:9577–9582
Schromm AB, Lien E, Henneke P, Chow JC, Yoshimura A, Heine H, Latz E, Monks BG, Schwartz DA, Miyake K, Golenbock DT (2001) Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling. J Exp Med 194: 79–88
Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Annu Rev Immunol 21:335–376
Takeuchi O, Hoshino K, Akira S (2000) Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J Immunol 165:5392–5396
Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 13: 933–940
Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, Modlin R, Akira S (2002) Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 169:10–14
Tochinai S, Katagiri C (1975) Complete abrogation of immune response to skin allo grafts and rabbit erythrocytes in the early thymectomized Xenopus. Dev Growth Differ 17(4):383–394
Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, Hieny S, Sutterwala FS, Flavell RA, Ghosh S, Sher A (2005) TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308: 1626–1629
Yilmaz A, Shen S, Adelson DL, Xavier S, Zhu JJ (2005) Identification and sequence analysis of chicken Toll-like receptors. Immunogenetics 56:743–753
Acknowledgment
This work was supported in part by CREST, JST (Japan Science and Technology oration) and by Grants-in-Aid from the Ministry of Education, Science, and Culture (Specified Project for Advanced Research) of Japan and by the Mitsubishi Foundation (TS), Takeda Foundation (TS) and Uehara Memorial Foundation (MM). Discussions with Dr. Oshiumi and Ms. Matsuo are gratefully acknowledged. Dr. V. Kumar reviewed this manuscript.
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Ishii, A., Kawasaki, M., Matsumoto, M. et al. Phylogenetic and expression analysis of amphibian Xenopus Toll-like receptors. Immunogenetics 59, 281–293 (2007). https://doi.org/10.1007/s00251-007-0193-y
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DOI: https://doi.org/10.1007/s00251-007-0193-y