Genomic Analyses of Toll-like Receptor 4 and 7 Exons of Bos indicus from Temperate Sub-himalayan Region of India
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Toll-like receptors (TLRs) play an important role in the recognition of invading pathogens and the modulation of innate immune responses in mammals. The TLR4 and TLR7 are well known to recognize the bacterial lipopolysaccharide (LPS) and single stranded (ssRNA) ligands, respectively and play important role in host defense against Gram-negative bacteria and ssRNA viruses. In the present study, coding exon fragments of these two TLRs were identified, cloned, sequenced and analyzed in terms of insertion-deletion polymorphism, within bovine TLRs 4 and 7, thereby facilitating future TLR signaling and association studies relevant to bovine innate immunity. Comparative sequence analysis of TLR 4 exons revealed that this gene is more variable, particularly the coding frame (E3P1), while other parts showed percent identity of 95.7% to 100% at nucleotide and amino acid level, respectivley with other Bos indicus and Bos taurus breeds from different parts of the world. In comparison to TLR4, sequence analysis of TLR7 showed more conservation among different B. indicus and B. taurus breeds, except single point mutation at 324 nucleotide position (AAA to AAM) altering a single amino acid at 108 position (K to X). Percent identity of TLR7 sequences (all 3 exons) was between 99.2% to 100% at nucleotide and amino acid level, when compared with available sequence database of B. indicus and B. taurus. Simple Modular Architecture Research Tool (SMART) analysis showed variations in the exon fragments located in the Leucine Rich Repeat (LRR) region, which is responsible for binding with the microbial associated molecular patterns and further, downstream signaling to initiate anti-microbial response. Considering importance of TLR polymorphism in terms of innate immunity, further research is warranted.
Abstract
Toll-like receptors (TLRs) play an important role in the recognition of invading pathogens and the modulation of innate immune responses in mammals. The TLR4 and TLR7 are well known to recognize the bacterial lipopolysaccharide (LPS) and single stranded (ssRNA) ligands, respectively and play important role in host defense against Gram-negative bacteria and ssRNA viruses. In the present study, coding exon fragments of these two TLRs were identified, cloned, sequenced and analyzed in terms of insertion-deletion polymorphism, within bovine TLRs 4 and 7, thereby facilitating future TLR signaling and association studies relevant to bovine innate immunity. Comparative sequence analysis of TLR 4 exons revealed that this gene is more variable, particularly the coding frame (E3P1), while other parts showed percent identity of 95.7% to 100% at nucleotide and amino acid level, respectivley with other Bos indicus and Bos taurus breeds from different parts of the world. In comparison to TLR4, sequence analysis of TLR7 showed more conservation among different B. indicus and B. taurus breeds, except single point mutation at 324 nucleotide position (AAA to AAM) altering a single amino acid at 108 position (K to X). Percent identity of TLR7 sequences (all 3 exons) was between 99.2% to 100% at nucleotide and amino acid level, when compared with available sequence database of B. indicus and B. taurus. Simple Modular Architecture Research Tool (SMART) analysis showed variations in the exon fragments located in the Leucine Rich Repeat (LRR) region, which is responsible for binding with the microbial associated molecular patterns and further, downstream signaling to initiate anti-microbial response. Considering importance of TLR polymorphism in terms of innate immunity, further research is warranted.
참고문헌 (25)
- Aderem, A, "Toll-like receptors in the induction of the innate immune responses", Nature, 406, pp.782~787 (2000)
- Akira, S, "Toll-like receptor signalling", Nat. Rev. Immunol, 4, pp.499~511 (2004)
- Akira, S., "Pathogen recognition and innate immunity", Cell, 124, pp.783~801 (2006)
- Barton, G. M, "Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA", Nat. Immunol, 7, pp.49~56 (2006)
- Beutler, B, "Evolution of TIR, tolls and TLRs: functional inferences from computational biology", Curr. Top. Microbiol. Immunol, 270, pp.1~21 (2002)
- Diebold, S. S, "Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA", Science, 303, pp.1529~1531 (2004)
- Hashimoto, C, "The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein", Cell, 52, pp.269~279 (1988)
- Janeway, Jr. C. A, "Innate immune recognition", Annu. Rev. Immunol, 20, pp.197~216 (2002)
- Jin, M. S, "Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide", CELL, 130, pp.1071~1082, CELL PRESS
- Keestra, A. M, "Functional characterization of chicken TLR5 reveals species-specific recognition of flagellin", Mol. Immunol, 45, pp.1298~1307 (2008)
- Lemaitre, B., "The dorsoventral regulatory gene cassette spatzle", Toll, Cell, pp.1996, 86[DOI]
- Loftus, R. T., "Evidence for two independent domestications of cattle", Proc. Natl. Acad. Sci. USA, 91, pp.2757~2761 (1994)
- Matsushima, N, "Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors", BMC Genomics, 8, pp.124~ (2007)
- Medzhitov, R, "Innate immunity", N. Engl. J. Med, 343, pp.338~344 (2000)
- Muzio, M, "Toll-like receptors: a growing family of immune receptors that are differentially expressed and regulated by different leukocytes", J. Leukoc. Biol, 67, pp.450~456 (2000)
- O’Neill, L. A, "TLRs: Professor Mechnikov, sit on your hat", Trends Immunol, 25, pp.687~693 (2004)
- Pandey, S, "Immunobiology of Toll-like receptors: Emerging trends", Immun. Cell Biol, 84, pp.333~341 (2006)
- Pasare, C, "Toll-like receptors: linking innate and adaptive immunity", Microbes Infect, 6, pp.1382~1387 (2004)
- Poltorak, A, "Physical contact between lipopolysaccharide and tolllike receptor 4 revealed by genetic complementation", Proc. Natl. Acad. Sci. USA, 97, pp.2163~2167 (2000)
- Schultz, J., "SMART: A Web-based tool for the study of genetically mobile domains", Nucleic Acids Res, 28, pp.231~234 (2000)
- Takeda, K, "Toll-like receptors", Annu. Rev. Immunol, 21, pp.335~376 (2003)
- Underhill, D. M, "Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages", Proc. Natl. Acad. Sci. USA, 96, pp.14459~14463 (1999)
- Weber, A. N. R, "Four Nlinked glycosylation sites in human Toll-like receptor 2 cooperate to direct efficient biosynthesis and secretion", J. Biol. Chem, 279, pp.34589~34594 (2004)
- West, A. P, "Recognition and signaling by Toll-like receptors", Annu. Rev. Cell Dev. Biol, 22, pp.409~437 (2006)
- Zhou, H, "Evolutionary analysis for functional divergence of the toll-like receptor gene family and altered functional constraints", J. Mol. Evol, 65, pp.119~123 (2007)