Induction of a novel chicken toll-like receptor following Salmonella enterica serovar Typhimurium infection

被引:153
作者
Higgs, R
Cormican, P
Cahalane, S
Allan, B
Lloyd, AT
Meade, K
James, T
Lynn, DJ
Babiuk, LA
O'Farrelly, C [1 ]
机构
[1] St Vincents Univ Hosp, Educ & Res Ctr, Dublin 4, Ireland
[2] Univ Coll Dublin, Dept Med, Dublin 4, Ireland
[3] Univ Coll Dublin, Conway Inst Biomed & Biomol Sci, Dublin 4, Ireland
[4] Univ Dublin Trinity Coll, Moyne Inst Prevent Med, Dublin 2, Ireland
[5] Univ Dublin Trinity Coll, Dept Genet, Dublin 2, Ireland
[6] Vaccine & Infect Dis Org, Saskatoon, SK S7N 5E3, Canada
关键词
D O I
10.1128/IAI.74.3.1692-1698.2006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Toll-like receptors (TLRs) are a group of highly conserved molecules that initiate the innate immune response to pathogens by recognizing structural motifs expressed by microbes. We have identified a novel TLR, TLR15, by bioinformatic analysis of the chicken genome, which is distinct from any known vertebrate TLR and thus appears to be avian specific. The gene for TLR15 was sequenced and is found on chromosome 3, and it has archetypal TIR and transmembrane domains and a distinctive arrangement of extracellular leucine-rich regions. mRNA for TLR15 was detected in the spleen, bursa, and bone marrow of healthy chickens, suggesting a role for this novel receptor in constitutive host defense. Following in vivo Salmonella enterica serovar Typhimurium infection, quantitative real-time PCR demonstrated significant upregulation of TLR15 in the cecum of infected chickens. Interestingly, similar induction of TLR2 expression following infection was also observed. In vitro studies revealed TLR15 upregulation in chicken embryonic fibroblasts stimulated with heat-killed S. enterica serovar Typhimurium. Collectively, these results suggest a role for the TLR in avian defense against bacterial infection. We hypothesize that TLR15 may represent an avian-specific TLR that has been either retained in chicken and lost in other taxa or gained in the chicken.
引用
收藏
页码:1692 / 1698
页数:7
相关论文
共 35 条
[1]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[2]   Mapping of the chicken and mouse genes for toll-like receptor 2 (TLR2) to an evolutionarily conserved chromosomal segment [J].
Boyd, Y ;
Goodchild, M ;
Morroll, S ;
Bumstead, N .
IMMUNOGENETICS, 2001, 52 (3-4) :294-298
[3]   Prediction of complete gene structures in human genomic DNA [J].
Burge, C ;
Karlin, S .
JOURNAL OF MOLECULAR BIOLOGY, 1997, 268 (01) :78-94
[4]   Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction [J].
Chow, JC ;
Young, DW ;
Golenbock, DT ;
Christ, WJ ;
Gusovsky, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (16) :10689-10692
[5]   MD-2 enables toll-like receptor 2 (TLR2)-mediated responses to lipopolysaccharide and enhances TLR2-mediated responses to gram-positive and gram-negative bacteria and their cell wall components [J].
Dziarski, R ;
Wang, QL ;
Miyake, K ;
Kirschning, CJ ;
Gupta, D .
JOURNAL OF IMMUNOLOGY, 2001, 166 (03) :1938-1944
[6]   Profile hidden Markov models [J].
Eddy, SR .
BIOINFORMATICS, 1998, 14 (09) :755-763
[7]   Molecular cloning and functional characterization of chicken toll-like receptors - A single chicken toll covers multiple molecular patterns [J].
Fuku, A ;
Inoue, N ;
Matsumoto, M ;
Nomura, M ;
Yamada, K ;
Matsuda, Y ;
Toyoshima, K ;
Seya, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (50) :47143-47149
[8]   Toll-like receptors as sensors of pathogens [J].
Hallman, M ;
Rämet, M ;
Ezekowitz, RA .
PEDIATRIC RESEARCH, 2001, 50 (03) :315-321
[9]   Identification and functional characterization of chicken Toll-like receptor 5 reveals a fundamental role in the biology of infection with Salmonella enterica serovar typhimurium [J].
Iqbal, M ;
Philbin, VJ ;
Withanage, GSK ;
Wigley, P ;
Beal, RK ;
Goodchild, MJ ;
Barrow, P ;
McConnell, I ;
Maskell, DJ ;
Young, J ;
Bumstead, N ;
Boyd, Y ;
Smith, AL .
INFECTION AND IMMUNITY, 2005, 73 (04) :2344-2350
[10]   Expression patterns of chicken Toll-like receptor mRNA in tissues, immune cell subsets and cell lines [J].
Iqbal, M ;
Philbin, VJ ;
Smith, AL .
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 2005, 104 (1-2) :117-127