Toll-Like Receptor Function and Evolution in Primates

Part of the Developments in Primatology: Progress and Prospects book series (DIPR)


Toll-like receptors (TLRs) are an important interface between vertebrate hosts and pathogens. From an evolutionary standpoint, these germline encoded receptors and their associated signaling pathways are interesting because they provide a window through which we can examine the relationships between primate environments, genomes, and immune responses. TLRs are key in host recognition of nonself and the activation of the innate immune response, a major determinant of host infection susceptibility and disease progression. TLR-initiated cell signaling not only forms an important part of host’s first line of defense against immune insult but also modulates adaptive immune responses. The efficacy of TLR-triggered immune responses has profound effects on host survival, with both overt and weak responses linked to host death. Despite sharing high genomic identity, primate species often manifest TLR-detected infectious pathogens differently (e.g., immunodeficiency viruses, Trypanosoma brucei, and Gram-negative bacteria). These differences suggest that primate TLR-triggered responses have diverged over time. In this chapter we review what is currently known about Toll-like receptor function and evolution in primates and discuss how studying the evolution of TLR-triggered immune responses may help explain disparities observed in microorganism-induced primate disease.


Innate Immune Response Rhesus Macaque Primate Species World Monkey Yersinia Pestis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abe K, Kagei N, Teramura Y, Ejima H (1993) Hepatocellular carcinoma associated with chronic Schistosoma mansoni infection in a chimpanzee. J Med Primatol 22(4):237–239PubMedGoogle Scholar
  2. Agnese DM, Calvano JE, Hahm SJ, Coyle SM, Corbett SA, Calvano SE, Lowry SF (2002) Human Toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections. J Infect Dis 186(10):1522–1525PubMedGoogle Scholar
  3. Alcaide M, Edwards SV (2011) Molecular evolution of the Toll-like receptor multigene family in birds. Mol Biol Evol 28(5):1703–1715PubMedGoogle Scholar
  4. 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(6857):732–738PubMedGoogle Scholar
  5. Aliprantis AO, Yang RB, Mark MR, Suggett S, Devaux B, Radolf JD, Klimpel GR, Godowski P, Zychlinsky A (1999) Cell activation and apoptosis by bacterial lipoproteins through Toll-like receptor-2. Science 285(5428):736–739PubMedGoogle Scholar
  6. Allikmets R, Buchbinder SP, Carrington M, Dean M, Detels R, Donfield S, Goedert JJ, Gomperts E, Huttley GA, Kaslow R et al (1996) Genetic restrictions of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273:1856–1862PubMedGoogle Scholar
  7. Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, Frees K, Watt JL, Schwartz DA (2000) TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 25(2):187–191PubMedGoogle Scholar
  8. Areal H, Abrantes J, Esteves PJ (2011) Signatures of positive selection in Toll-like receptor (TLR) genes in mammals. BMC Evol Biol 11:368PubMedCentralPubMedGoogle Scholar
  9. Arko RJ (1989) Animal models for pathogenic Neisseria species. Clin Microbiol Rev 2(Suppl):S56–59PubMedCentralPubMedGoogle Scholar
  10. Bafica A, Santiago HC, Goldszmid R, Ropert C, Gazzinelli RT, Sher A (2006) Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection. J Immunol 177(6):3515–3519PubMedGoogle Scholar
  11. Barber RC, Chang LY, Arnoldo BD, Purdue GF, Hunt JL, Horton JW, Aragaki CC (2006) Innate immunity SNPs are associated with risk for severe sepsis after burn injury. Clin Med Res 4(4):250–255PubMedCentralPubMedGoogle Scholar
  12. Barreiro LB, Quintana-Murci L (2010) From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet 11(1):17–30PubMedGoogle Scholar
  13. Barreiro LB, Ben-Ali M, Quach H, Laval G, Patin E, Pickrell JK, Bouchier C, Tichit M, Neyrolles O, Gicquel B et al (2009) Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet 5(7):e1000562PubMedCentralPubMedGoogle Scholar
  14. Barreiro LB, Marioni JC, Blekhman R, Stephens M, Gilad Y (2010) Functional comparison of innate immune signaling pathways in primates. PLoS Genet 6(12):e1001249PubMedCentralPubMedGoogle Scholar
  15. Barrett RD, Hoekstra HE (2011) Molecular spandrels: tests of adaptation at the genetic level. Nat Rev Genet 12(11):767–780PubMedGoogle Scholar
  16. Ben-Ali M, Corre B, Manry J, Barreiro LB, Quach H, Boniotto M, Pellegrini S, Quintana-Murci L (2011) Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family. Hum Mutat 32(6):643–652PubMedGoogle Scholar
  17. Benveniste RE, Arthur LO, Tsai CC, Sowder R, Copeland TD, Henderson LE, Oroszlan S (1986) Isolation of a lentivirus from a macaque with lymphoma: comparison with HTLV-III/LAV and other lentiviruses. J Virol 60(2):483–490PubMedCentralPubMedGoogle Scholar
  18. Bettauer RH (2010) Chimpanzees in hepatitis C virus research: 1998–2007. J Med Primatol 39(1):9–23PubMedGoogle Scholar
  19. Biraben JN (1975) Les hommes et la peste en France et dans les pays européens et méditerranéens. Mouton, ParisGoogle Scholar
  20. Blackwell TS, Christman JW (1996) Sepsis and cytokines: current status. Br J Anaesth 77(1): 110–117PubMedGoogle Scholar
  21. Bochud P-Y, Hersberger M, Taffe P, Bochud M, Stein CM, Rodrigues SD, Calandra T, Francioli P, Telenti A, Speck RF et al (2007) Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection. AIDS 21(4):441–446, 410.1097/QAD.1090b1013e328012b328018acPubMedGoogle Scholar
  22. Bochud PY, Hawn TR, Siddiqui MR, Saunderson P, Britton S, Abraham I, Argaw AT, Janer M, Zhao LP, Kaplan G et al (2008) Toll-like receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy. J Infect Dis 197(2):253–261PubMedCentralPubMedGoogle Scholar
  23. Bosinger SE, Sodora DL, Silvestri G (2011) Generalized immune activation and innate immune responses in simian immunodeficiency virus infection. Curr Opin HIV AIDS 6(5):411–418PubMedCentralPubMedGoogle Scholar
  24. Bouer A, Werther K, Machado RZ, Nakaghi AC, Epiphanio S, Catao-Dias JL (2010) Detection of anti-Toxoplasma gondii antibodies in experimentally and naturally infected non-human primates by Indirect Fluorescence Assay (IFA) and indirect ELISA. Rev Bras Parasitol Vet 19(1):26–31PubMedGoogle Scholar
  25. Brinkworth J, Pechenkina E, Silver J, Goyert S (2012) Innate immune responses to TLR2 and TLR4 agonists differ between baboons, chimpanzees and humans. J Med Primatol 41:388–393PubMedCentralPubMedGoogle Scholar
  26. Brown WJ, Lucas CT, Kuhn US (1972) Gonorrhoea in the chimpanzee. Infection with laboratory-passed gonococci and by natural transmission. Br J Vener Dis 48(3):177–178PubMedCentralPubMedGoogle Scholar
  27. Bulut Y, Faure E, Thomas L, Equils O, Arditi M (2001) Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J Immunol 167(2):987–994PubMedGoogle Scholar
  28. Buwitt-Beckmann U, Heine H, Wiesmuller KH, Jung G, Brock R, Akira S, Ulmer AJ (2005) Toll-like receptor 6-independent signaling by diacylated lipopeptides. Eur J Immunol 35(1):282–289PubMedGoogle Scholar
  29. Campos MA, Almeida IC, Takeuchi O, Akira S, Valente EP, Procopio DO, Travassos LR, Smith JA, Golenbock DT, Gazzinelli RT (2001) Activation of Toll-like receptor-2 by glycosylphosphatidylinositol anchors from a protozoan parasite. J Immunol 167(1):416–423PubMedGoogle Scholar
  30. Catão-Dias JL, Epiphanio S, Martins Kierulff MC (2013) Neotropical primates and their susceptibility to Toxoplasma gondii: new insights for an old problem. In: Brinkworth JF, Pechenkina E (eds) Primates, pathogens, and evolution. Springer, HeidelbergGoogle Scholar
  31. Cerf-Bensussan N, Gaboriau-Routhiau V (2010) The immune system and the gut microbiota: friends or foes? Nat Rev Immunol 10(10):735–744PubMedGoogle Scholar
  32. Dabbagh K, Dahl ME, Stepick-Biek P, Lewis DB (2002) Toll-like receptor 4 is required for optimal development of Th2 immune responses: role of dendritic cells. J Immunol 168(9):4524–4530PubMedGoogle Scholar
  33. Daniel MD, King NW, Letvin NL, Hunt RD, Sehgal PK, Desrosiers RC (1984) A new type D retrovirus isolated from macaques with an immunodeficiency syndrome. Science 223(4636):602–605PubMedGoogle Scholar
  34. De Vos R, Verslype C, Depla E, Fevery J, Van Damme B, Desmet V, Roskams T (2002) Ultrastructural visualization of hepatitis C virus components in human and primate liver biopsies. J Hepatol 37(3):370–379PubMedGoogle Scholar
  35. Dean AM, Thornton JW (2007) Mechanistic approaches to the study of evolution: the functional synthesis. Nat Rev Genet 8(9):675–688PubMedCentralPubMedGoogle Scholar
  36. Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittinghoff E, Gomperts E et al (1996) Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 273(5283):1856–1862PubMedGoogle Scholar
  37. Debierre-Grockiego F, Campos MA, Azzouz N, Schmidt J, Bieker U, Resende MG, Mansur DS, Weingart R, Schmidt RR, Golenbock DT et al (2007) Activation of TLR2 and TLR4 by glycosylphosphatidylinositols derived from Toxoplasma gondii. J Immunol 179(2):1129–1137PubMedGoogle Scholar
  38. Delport W, Poon AF, Frost SD, Kosakovsky Pond SL (2010) Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology. Bioinformatics 26(19):2455–2457PubMedCentralPubMedGoogle Scholar
  39. Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303(5663):1529–1531PubMedGoogle Scholar
  40. Elvin SJ, Williamson ED, Scott JC, Smith JN, Perez De Lema G, Chilla S, Clapham P, Pfeffer K, Schlondorff D, Luckow B (2004) Evolutionary genetics: ambiguous role of CCR5 in Y. pestis infection. Nature 430(6998):417PubMedGoogle Scholar
  41. Epiphanio S, Sinhorini IL, Catao-Dias JL (2003) Pathology of toxoplasmosis in captive new world primates. J Comp Pathol 129(2–3):196–204PubMedGoogle Scholar
  42. Esposito S, Molteni CG, Zampiero A, Baggi E, Lavizzari A, Semino M, Daleno C, Groppo M, Scala A, Terranova L et al (2012) Role of polymorphisms of Toll-like receptor (TLR) 4, TLR9, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A genes in malaria susceptibility and severity in Burundian children. Malar J 11:196PubMedCentralPubMedGoogle Scholar
  43. Estep RD, Messaoudi I, Wong SW (2010) Simian herpesviruses and their risk to humans. Vaccine 28(Suppl 2):B78–84PubMedGoogle Scholar
  44. Etienne L, Nerrienet E, LeBreton M, Bibila GT, Foupouapouognigni Y, Rousset D, Nana A, Djoko CF, Tamoufe U, Aghokeng AF et al (2011) Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms. Retrovirology 8:4PubMedCentralPubMedGoogle Scholar
  45. Farah IO, Mola PW, Kariuki TM, Nyindo M, Blanton RE, King CL (2000) Repeated exposure induces periportal fibrosis in Schistosoma mansoni-infected baboons: role of TGF-beta and IL-4. J Immunol 164(10):5337–5343PubMedGoogle Scholar
  46. Farah IO, Kariuki TM, King CL, Hau J (2001) An overview of animal models in experimental schistosomiasis and refinements in the use of non-human primates. Lab Anim 35(3):205–212PubMedGoogle Scholar
  47. Ferrer-Admetlla A, Bosch E, Sikora M, Marques-Bonet T, Ramirez-Soriano A, Muntasell A, Navarro A, Lazarus R, Calafell F, Bertranpetit J et al (2008) Balancing selection is the main force shaping the evolution of innate immunity genes. J Immunol 181(2):1315–1322PubMedGoogle Scholar
  48. Ferwerda B, McCall MB, Verheijen K, Kullberg BJ, van der Ven AJ, Van der Meer JW, Netea MG (2008) Functional consequences of Toll-like receptor 4 polymorphisms. Mol Med 14(5–6): 346–352PubMedCentralPubMedGoogle Scholar
  49. Feterowski C, Emmanuilidis K, Miethke T, Gerauer K, Rump M, Ulm K, Holzmann B, Weighardt H (2003) Effects of functional Toll-like receptor-4 mutations on the immune response to human and experimental sepsis. Immunology 109(3):426–431PubMedCentralPubMedGoogle Scholar
  50. Fischer E, Marano MA, Barber AE, Hudson A, Lee K, Rock CS, Hawes AS, Thompson RC, Hayes TJ, Anderson TD et al (1991) Comparison between effects of interleukin-1 alpha administration and sublethal endotoxemia in primates. Am J Physiol 261(2 Pt 2):R442–452PubMedGoogle Scholar
  51. Flynn JL, Capuano SV, Croix D, Pawar S, Myers A, Zinovik A, Klein E (2003) Non-human primates: a model for tuberculosis research. Tuberculosis (Edinb) 83(1–3):116–118Google Scholar
  52. Fumagalli M, Sironi M, Pozzoli U, Ferrer-Admetlla A, Pattini L, Nielsen R (2011) Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution. PLoS Genet 7(11):e1002355PubMedCentralPubMedGoogle Scholar
  53. Gage KL, Kosoy MY (2005) Natural history of plague: perspectives from more than a century of research. Annu Rev Entomol 50:505–528PubMedGoogle Scholar
  54. Galvani AP, Slatkin M (2003) Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele. Proc Natl Acad Sci USA 100(25):15276–15279PubMedCentralPubMedGoogle Scholar
  55. Garcia MA, Yee J, Bouley DM, Moorhead R, Lerche NW (2004) Diagnosis of tuberculosis in macaques, using whole-blood in vitro interferon-gamma (PRIMAGAM) testing. Comp Med 54(1):86–92PubMedGoogle Scholar
  56. Gioannini TL, Teghanemt A, Zhang D, Coussens NP, Dockstader W, Ramaswamy S, Weiss JP (2004) Isolation of an endotoxin-MD-2 complex that produces Toll-like receptor 4-dependent cell activation at picomolar concentrations. Proc Natl Acad Sci USA 101(12):4186–4191PubMedCentralPubMedGoogle Scholar
  57. Gottfried R (1983) The black death: natural and human disaster in medieval Europe. Free Press, New York, p 203Google Scholar
  58. Gutierrez MC, Brisse S, Brosch R, Fabre M, Omais B, Marmiesse M, Supply P, Vincent V (2005) Ancient origin and gene mosaicism of the progenitor of Mycobacterium tuberculosis. PLoS Pathog 1(1):e5PubMedCentralPubMedGoogle Scholar
  59. Haensch S, Bianucci R, Signoli M, Rajerison M, Schultz M, Kacki S, Vermunt M, Weston DA, Hurst D, Achtman M et al (2010) Distinct clones of Yersinia pestis caused the black death. PLoS Pathog 6(10):e1001134PubMedCentralPubMedGoogle Scholar
  60. Hagberg L, Hull R, Hull S, McGhee JR, Michalek SM, Svanborg EC (1984) Difference in susceptibility to gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice. Infect Immun 46(3):839–844PubMedCentralPubMedGoogle Scholar
  61. Haudek SB, Natmessnig BE, Furst W, Bahrami S, Schlag G, Redl H (2003) Lipopolysaccharide dose response in baboons. Shock 20(5):431–436PubMedGoogle Scholar
  62. Hawn TR, Verbon A, Lettinga KD, Zhao LP, Li SS, Laws RJ, Skerrett SJ, Beutler B, Schroeder L, Nachman A et al (2003) A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires’ disease. J Exp Med 198(10):1563–1572PubMedCentralPubMedGoogle Scholar
  63. Hawn TR, Verbon A, Janer M, Zhao LP, Beutler B, Aderem A (2005) Toll-like receptor 4 polymorphisms are associated with resistance to Legionnaires’ disease. Proc Natl Acad Sci USA 102(7):2487–2489PubMedCentralPubMedGoogle Scholar
  64. Hawn TR, Misch EA, Dunstan SJ, Thwaites GE, Lan NT, Quy HT, Chau TT, Rodrigues S, Nachman A, Janer M et al (2007) A common human TLR1 polymorphism regulates the innate immune response to lipopeptides. Eur J Immunol 37(8):2280–2289PubMedGoogle Scholar
  65. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410(6832):1099–1103PubMedGoogle Scholar
  66. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S (2004) Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303(5663):1526–1529PubMedGoogle Scholar
  67. 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(2):196–200PubMedGoogle Scholar
  68. 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(7):3749–3752PubMedGoogle Scholar
  69. Jallow M, Teo YY, Small KS, Rockett KA, Deloukas P, Clark TG, Kivinen K, Bojang KA, Conway DJ, Pinder M et al (2009) Genome-wide and fine-resolution association analysis of malaria in West Africa. Nat Genet 41(6):657–665PubMedCentralPubMedGoogle Scholar
  70. Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216PubMedGoogle Scholar
  71. Jin MS, Lee J-O (2008) Structures of the Toll-like receptor family and its ligand complexes. Immunity 29(2):182–191PubMedGoogle Scholar
  72. Johnson CM, Lyle EA, Omueti KO, Stepensky VA, Yegin O, Alpsoy E, Hamann L, Schumann RR, Tapping RI (2007) Cutting edge: a common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. J Immunol 178(12):7520–7524PubMedGoogle Scholar
  73. Kang TJ, Lee SB, Chae GT (2002) A polymorphism in the Toll-like receptor 2 is associated with IL-12 production from monocyte in lepromatous leprosy. Cytokine 20(2):56–62PubMedGoogle Scholar
  74. Kawai T, Akira S (2007) TLR signaling. Semin Immunol 19(1):24–32PubMedGoogle Scholar
  75. Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11(5):373–384PubMedGoogle Scholar
  76. Keele BF, Jones JH, Terio KA, Estes JD, Rudicell RS, Wilson ML, Li Y, Learn GH, Beasley TM, Schumacher-Stankey J et al (2009) Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz. Nature 460(7254):515–519PubMedCentralPubMedGoogle Scholar
  77. Krieg AM (2007) Antiinfective applications of Toll-like receptor 9 agonists. Proc Am Thorac Soc 4(3):289–294PubMedCentralPubMedGoogle Scholar
  78. Kumar H, Kawai T, Akira S (2009) Pathogen recognition in the innate immune response. Biochem J 420(1):1–16PubMedGoogle Scholar
  79. Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, Walsh EE, Freeman MW, Golenbock DT, Anderson LJ et al (2000) Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol 1(5):398–401PubMedGoogle Scholar
  80. Kurt-Jones EA, Chan M, Zhou S, Wang J, Reed G, Bronson R, Arnold MM, Knipe DM, Finberg RW (2004) Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci USA 101(5):1315–1320PubMedCentralPubMedGoogle Scholar
  81. Langermans JA, Andersen P, van Soolingen D, Vervenne RA, Frost PA, van der Laan T, van Pinxteren LA, van den Hombergh J, Kroon S, Peekel I et al (2001) Divergent effect of bacillus Calmette-Guerin (BCG) vaccination on Mycobacterium tuberculosis infection in highly related macaque species: implications for primate models in tuberculosis vaccine research. Proc Natl Acad Sci USA 98(20):11497–11502PubMedCentralPubMedGoogle Scholar
  82. Lorenz E, Mira JP, Frees KL, Schwartz DA (2002) Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch Intern Med 162(9):1028–1032PubMedGoogle Scholar
  83. Lucas CT, Chandler F Jr, Martin JE Jr, Schmale JD (1971) Transfer of gonococcal urethritis from man to chimpanzee. An animal model for gonorrhea. JAMA 216(10):1612–1614PubMedGoogle Scholar
  84. Lucotte G (2001) Distribution of the CCR5 gene 32-basepair deletion in West Europe. A hypothesis about the possible dispersion of the mutation by the Vikings in historical times. Hum Immunol 62(9):933–936PubMedGoogle Scholar
  85. Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA (2004) Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 101(15):5598–5603PubMedCentralPubMedGoogle Scholar
  86. Ma X, Liu Y, Gowen BB, Graviss EA, Clark AG, Musser JM (2007a) Full-exon resequencing reveals Toll-like receptor variants contribute to human susceptibility to tuberculosis disease. PLoS One 2(12):e1318PubMedCentralPubMedGoogle Scholar
  87. Ma Y, Haynes RL, Sidman RL, Vartanian T (2007b) TLR8: an innate immune receptor in brain, neurons and axons. Cell Cycle 6(23):2859–2868PubMedGoogle Scholar
  88. Major ME, Dahari H, Mihalik K, Puig M, Rice CM, Neumann AU, Feinstone SM (2004) Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees. Hepatology 39(6):1709–1720PubMedGoogle Scholar
  89. Mandl JN, Barry AP, Vanderford TH, Kozyr N, Chavan R, Klucking S, Barrat FJ, Coffman RL, Staprans SI, Feinberg MB (2008) Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med 14(10):1077–1087PubMedGoogle Scholar
  90. Mandl JN, Akondy R, Lawson B, Kozyr N, Staprans SI, Ahmed R, Feinberg MB (2011) Distinctive TLR7 signaling, type I IFN production, and attenuated innate and adaptive immune responses to yellow fever virus in a primate reservoir host. J Immunol 186(11):6406–6416PubMedGoogle Scholar
  91. Martin R (2003) Earth history, disease, and the evolution of primates. In: Greenblatt C, Spigelmann M (eds) Emerging pathogens: archaeology, ecology and evolution of infectious disease. Oxford University Press, New YorkGoogle Scholar
  92. Massari P, Henneke P, Ho Y, Latz E, Golenbock DT, Wetzler LM (2002) Cutting edge: immune stimulation by neisserial porins is Toll-like receptor 2 and MyD88 dependent. J Immunol 168(4):1533–1537PubMedGoogle Scholar
  93. Matsushima N, Tanaka T, Enkhbayar P, Mikami T, Taga M, Yamada K, Kuroki Y (2007) Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate Toll-like receptors. BMC Genomics 8:124PubMedCentralPubMedGoogle Scholar
  94. Matsuura M, Takahashi H, Watanabe H, Saito S, Kawahara K (2010) Immunomodulatory effects of Yersinia pestis lipopolysaccharides on human macrophages. Clin Vaccine Immunol 17(1):49–55PubMedCentralPubMedGoogle Scholar
  95. McGee ZA, Stephens DS, Hoffman LH, Schlech WF 3rd, Horn RG (1983) Mechanisms of mucosal invasion by pathogenic Neisseria. Rev Infect Dis 5(Suppl 4):S708–714PubMedGoogle Scholar
  96. McGee ZA, Gregg CR, Johnson AP, Kalter SS, Taylor-Robinson D (1990) The evolutionary watershed of susceptibility to gonococcal infection. Microb Pathog 9(2):131–139PubMedGoogle Scholar
  97. Means TK, Jones BW, Schromm AB, Shurtleff BA, Smith JA, Keane J, Golenbock DT, Vogel SN, Fenton MJ (2001) Differential effects of a Toll-like receptor antagonist on Mycobacterium tuberculosis-induced macrophage responses. J Immunol 166(6):4074–4082PubMedGoogle Scholar
  98. Mecsas J, Franklin G, Kuziel WA, Brubaker RR, Falkow S, Mosier DE (2004) Evolutionary genetics: CCR5 mutation and plague protection. Nature 427(6975):606PubMedGoogle Scholar
  99. Mir KD, Bosinger SE, Gasper M, Ho O, Else JG, Brenchley JM, Kelvin DJ, Silvestri G, Hu SL, Sodora DL (2012) Simian immunodeficiency virus-induced alterations in monocyte production of tumor necrosis factor alpha contribute to reduced immune activation in sooty mangabeys. J Virol 86(14):7605–7615PubMedCentralPubMedGoogle Scholar
  100. Montali RJ, Mikota SK, Cheng LI (2001) Mycobacterium tuberculosis in zoo and wildlife species. Rev Sci Tech 20(1):291–303PubMedGoogle Scholar
  101. Morelli G, Song Y, Mazzoni CJ, Eppinger M, Roumagnac P, Wagner DM, Feldkamp M, Kusecek B, Vogler AJ, Li Y et al (2010) Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nat Genet 42(12):1140–1143PubMedCentralPubMedGoogle Scholar
  102. Mukherjee S, Sarkar-Roy N, Wagener DK, Majumder PP (2009) Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature. Proc Natl Acad Sci USA 106(17):7073–7078PubMedCentralPubMedGoogle Scholar
  103. Murdoch C, Finn A (2003) The role of chemokines in sepsis and septic shock. Contrib Microbiol 10:38–57PubMedGoogle Scholar
  104. Nakajima T, Ohtani H, Satta Y, Uno Y, Akari H, Ishida T, Kimura A (2008) Natural selection in the TLR-related genes in the course of primate evolution. Immunogenetics 60(12):727–735PubMedGoogle Scholar
  105. Ngampasutadol J, Tran C, Gulati S, Blom AM, Jerse EA, Ram S, Rice PA (2008) Species-specificity of Neisseria gonorrhoeae infection: do human complement regulators contribute? Vaccine 26(Suppl 8):I62–66PubMedGoogle Scholar
  106. Nielsen R, Bustamante C, Clark AG, Glanowski S, Sackton TB, Hubisz MJ, Fledel-Alon A, Tanenbaum DM, Civello D, White TJ et al (2005) A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol 3(6):e170PubMedCentralPubMedGoogle Scholar
  107. Ogus AC, Yoldas B, Ozdemir T, Uguz A, Olcen S, Keser I, Coskun M, Cilli A, Yegin O (2004) The Arg753GLn polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease. Eur Respir J 23(2):219–223PubMedGoogle Scholar
  108. Oh DY, Taube S, Hamouda O, Kucherer C, Poggensee G, Jessen H, Eckert JK, Neumann K, Storek A, Pouliot M et al (2008) A functional Toll-like receptor 8 variant is associated with HIV disease restriction. J Infect Dis 198(5):701–709PubMedGoogle Scholar
  109. Oh DY, Baumann K, Hamouda O, Eckert JK, Neumann K, Kucherer C, Bartmeyer B, Poggensee G, Oh N, Pruss A et al (2009) A frequent functional Toll-like receptor 7 polymorphism is associated with accelerated HIV-1 disease progression. AIDS 23(3):297–307PubMedGoogle Scholar
  110. Ohashi K, Burkart V, Flohe S, Kolb H (2000) Cutting edge: heat shock protein 60 is a putative endogenous ligand of the Toll-like receptor-4 complex. J Immunol 164(2):558–561PubMedGoogle Scholar
  111. Omueti KO, Mazur DJ, Thompson KS, Lyle EA, Tapping RI (2007) The polymorphism P315L of human Toll-like receptor 1 impairs innate immune sensing of microbial cell wall components. J Immunol 178(10):6387–6394PubMedGoogle Scholar
  112. Onlamoon N, Noisakran S, Hsiao HM, Duncan A, Villinger F, Ansari AA, Perng GC (2010) Dengue virus-induced hemorrhage in a nonhuman primate model. Blood 115(9):1823–1834PubMedCentralPubMedGoogle Scholar
  113. Orange JS, Geha RS (2003) Finding NEMO: genetic disorders of NF-[kappa]B activation. J Clin Invest 112(7):983–985PubMedCentralPubMedGoogle Scholar
  114. Ortiz M, Kaessmann H, Zhang K, Bashirova A, Carrington M, Quintana-Murci L, Telenti A (2008) The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates. Genes Immun 9(6):483–492PubMedCentralPubMedGoogle Scholar
  115. 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(25): 13766–13771PubMedCentralPubMedGoogle Scholar
  116. Palm NW, Medzhitov R (2009) Pattern recognition receptors and control of adaptive immunity. Immunol Rev 227(1):221–233PubMedGoogle Scholar
  117. Pandrea I, Apetrei C (2010) Where the wild things are: pathogenesis of SIV infection in African nonhuman primate hosts. Curr HIV/AIDS Rep 7(1):28–36PubMedCentralPubMedGoogle Scholar
  118. Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO (2009) The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458(7242):1191–1195PubMedGoogle Scholar
  119. Payne KS, Novak JJ, Jongsakul K, Imerbsin R, Apisitsaowapa Y, Pavlin JA, Hinds SB (2011) Mycobacterium tuberculosis infection in a closed colony of rhesus macaques (Macaca mulatta). J Am Assoc Lab Anim Sci 50(1):105–108PubMedCentralPubMedGoogle Scholar
  120. Plantinga TS, Ioana M, Alonso S, Izagirre N, Hervella M, Joosten LA, van der Meer JW, de la Rua C, Netea MG (2012) The evolutionary history of TLR4 polymorphisms in Europe. J Innate Immun 4(2):168–175PubMedGoogle Scholar
  121. Pollitzer R (1951) Plague studies. 1. A summary of the history and survey of the present distribution of the disease. Bull World Health Organ 4(4):475–533PubMedCentralPubMedGoogle Scholar
  122. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C et al (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282(5396):2085–2088PubMedGoogle Scholar
  123. Pond SL, Frost SD (2005) Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 21(10):2531–2533PubMedGoogle Scholar
  124. Puel A, Picard C, Ku CL, Smahi A, Casanova JL (2004) Inherited disorders of NF-kappaB-mediated immunity in man. Curr Opin Immunol 16(1):34–41PubMedGoogle Scholar
  125. Quesniaux VJ, Nicolle DM, Torres D, Kremer L, Guerardel Y, Nigou J, Puzo G, Erard F, Ryffel B (2004) Toll-like receptor 2 (TLR2)-dependent-positive and TLR2-independent-negative regulation of proinflammatory cytokines by mycobacterial lipomannans. J Immunol 172(7):4425–4434PubMedGoogle Scholar
  126. Qureshi ST, Lariviere L, Leveque G, Clermont S, Moore KJ, Gros P, Malo D (1999) Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J Exp Med 189(4):615–625PubMedCentralPubMedGoogle Scholar
  127. Rayner JC, Liu W, Peeters M, Sharp PM, Hahn BH (2011) A plethora of Plasmodium species in wild apes: a source of human infection? Trends Parasitol 27(5):222–229PubMedCentralPubMedGoogle Scholar
  128. Redl H, Bahrami S, Schlag G, Traber DL (1993) Clinical detection of LPS and animal models of endotoxemia. Immunobiology 187(3–5):330–345PubMedGoogle Scholar
  129. 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(27):9577–9582PubMedCentralPubMedGoogle Scholar
  130. Rutz M, Metzger J, Gellert T, Luppa P, Lipford GB, Wagner H, Bauer S (2004) Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. Eur J Immunol 34(9):2541–2550PubMedGoogle Scholar
  131. Sadun EH, von Lichtenberg F, Cheever AW, Erickson DG (1970) Schistosomiasis mansoni in the chimpanzee. The natural history of chronic infections after single and multiple exposures. Am J Trop Med Hyg 19(2):258–277PubMedGoogle Scholar
  132. Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C et al (1996) Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382(6593):722–725PubMedGoogle Scholar
  133. Sapolsky RM, Else JG (1987) Bovine tuberculosis in a wild baboon population: epidemiological aspects. J Med Primatol 16(4):229–235PubMedGoogle Scholar
  134. Schott E, Witt H, Neumann K, Taube S, Oh DY, Schreier E, Vierich S, Puhl G, Bergk A, Halangk J et al (2007) A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV-infection. J Hepatol 47(2):203–211PubMedGoogle Scholar
  135. Schroder NW, Diterich I, Zinke A, Eckert J, Draing C, von Baehr V, Hassler D, Priem S, Hahn K, Michelsen KS et al (2005) Heterozygous Arg753Gln polymorphism of human TLR-2 impairs immune activation by Borrelia burgdorferi and protects from late stage Lyme disease. J Immunol 175(4):2534–2540PubMedGoogle Scholar
  136. Schuenemann VJ, Bos K, Dewitte S, Schmedes S, Jamieson J, Mittnik A, Forrest S, Coombes BK, Wood JW, Earn DJ et al (2011) From the cover: targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death. Proc Natl Acad Sci USA 108(38):E746–752PubMedCentralPubMedGoogle Scholar
  137. Schuring RP, Hamann L, Faber WR, Pahan D, Richardus JH, Schumann RR, Oskam L (2009) Polymorphism N248S in the human Toll-like receptor 1 gene is related to leprosy and leprosy reactions. J Infect Dis 199(12):1816–1819PubMedGoogle Scholar
  138. Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ (1999) Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2. J Biol Chem 274(25):17406–17409PubMedGoogle Scholar
  139. Shi Q, Wang J, Wang XL, VandeBerg JL (2004) Comparative analysis of vascular endothelial cell activation by TNF-alpha and LPS in humans and baboons. Cell Biochem Biophys 40(3):289–303PubMedGoogle Scholar
  140. Shi Q, Cox LA, Glenn J, Tejero ME, Hondara V, Vandeberg JL, Wang XL (2010) Molecular pathways mediating differential responses to lipopolysaccharide between human and baboon arterial endothelial cells. Clin Exp Pharmacol Physiol 37(2):178–184PubMedCentralPubMedGoogle Scholar
  141. Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 189(11):1777–1782PubMedCentralPubMedGoogle Scholar
  142. Siddiqui RA, Krawczak M, Platzer M, Sauermann U (2011) Association of TLR7 variants with AIDS-like disease and AIDS vaccine efficacy in rhesus macaques. PLoS One 6(10):e25474PubMedCentralPubMedGoogle Scholar
  143. Sing A, Rost D, Tvardovskaia N, Roggenkamp A, Wiedemann A, Kirschning CJ, Aepfelbacher M, Heesemann J (2002) Yersinia V-antigen exploits Toll-like receptor 2 and CD14 for interleukin 10-mediated immunosuppression. J Exp Med 196(8):1017–1024PubMedCentralPubMedGoogle Scholar
  144. Stephens JC, Reich DE, Goldstein DB, Shin HD, Smith MW, Carrington M, Winkler C, Huttley GA, Allikmets R, Schriml L et al (1998) Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes. Am J Hum Genet 62(6):1507–1515PubMedCentralPubMedGoogle Scholar
  145. Sterner KN, Weckle A, Chugani HT, Tarca AL, Sherwood CC, Hof PR, Kuzawa CW, Boddy AM, Abbas A, Raaum RL et al (2012) Dynamic gene expression in the human cerebral cortex distinguishes children from adults. PLoS One 7(5):e37714PubMedCentralPubMedGoogle Scholar
  146. Tada H, Nemoto E, Shimauchi H, Watanabe T, Mikami T, Matsumoto T, Ohno N, Tamura H, Shibata K, Akashi S et al (2002) Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14- and Toll-like receptor 4-dependent manner. Microbiol Immunol 46(7):503–512PubMedGoogle Scholar
  147. Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, Takeda K, Akira S (1999) Differential roles of TLR2 and TLR4 in recognition of Gram-negative and gram-positive bacterial cell wall components. Immunity 11(4):443–451PubMedGoogle Scholar
  148. Tarara R, Suleman MA, Sapolsky R, Wabomba MJ, Else JG (1985) Tuberculosis in wild olive baboons, Papio cynocephalus anubis (Lesson), in Kenya. J Wildl Dis 21(2):137–140PubMedGoogle Scholar
  149. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, Miyake K, Freudenberg M, Galanos C, Simon JC (2002) Oligosaccharides of Hyaluronan activate dendritic cells via Toll-like receptor 4. J Exp Med 195(1):99–111PubMedCentralPubMedGoogle Scholar
  150. Thomson M, Nascimbeni M, Havert MB, Major M, Gonzales S, Alter H, Feinstone SM, Murthy KK, Rehermann B, Liang TJ (2003) The clearance of hepatitis C virus infection in chimpanzees may not necessarily correlate with the appearance of acquired immunity. J Virol 77(2):862–870PubMedCentralPubMedGoogle Scholar
  151. Triantafilou M, Uddin A, Maher S, Charalambous N, Hamm TS, Alsumaiti A, Triantafilou K (2007) Anthrax toxin evades Toll-like receptor recognition, whereas its cell wall components trigger activation via TLR2/6 heterodimers. Cell Microbiol 9(12):2880–2892PubMedGoogle Scholar
  152. Underhill DM, Ozinsky A, Smith KD, Aderem A (1999) Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci USA 96(25):14459–14463PubMedCentralPubMedGoogle Scholar
  153. van der Kleij D, Latz E, Brouwers JF, Kruize YC, Schmitz M, Kurt-Jones EA, Espevik T, de Jong EC, Kapsenberg ML, Golenbock DT et al (2002) A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J Biol Chem 277(50):48122–48129PubMedGoogle Scholar
  154. van der Poll T, Levi M, van Deventer SJ, ten Cate H, Haagmans BL, Biemond BJ, Buller HR, Hack CE, ten Cate JW (1994) Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 83(2):446–451PubMedGoogle Scholar
  155. Vasl J, Prohinar P, Gioannini TL, Weiss JP, Jerala R (2008) Functional activity of MD-2 polymorphic variant is significantly different in soluble and TLR4-bound forms: decreased endotoxin binding by G56R MD-2 and its rescue by TLR4 ectodomain. J Immunol 180(9):6107–6115PubMedGoogle Scholar
  156. Vignal C, Guerardel Y, Kremer L, Masson M, Legrand D, Mazurier J, Elass E (2003) Lipomannans, but not lipoarabinomannans, purified from Mycobacterium chelonae and Mycobacterium kansasii induce TNF-alpha and IL-8 secretion by a CD14-Toll-like receptor 2-dependent mechanism. J Immunol 171(4):2014–2023PubMedGoogle Scholar
  157. Vitone N, Altizer S, Nunn CL (2004) Body size, diet and sociality influence the species richness of parasitic worms in anthropoid primates. Evol Ecol Res 6:183–199Google Scholar
  158. Vodros D, Fenyo EM (2004) Primate models for human immunodeficiency virus infection. Evolution of receptor use during pathogenesis. Acta Microbiol Immunol Hung 51(1–2):1–29PubMedGoogle Scholar
  159. von Bulow GU, Puren AJ, Savage N (1992) Interleukin-1 from baboon peripheral blood monocytes: altered response to endotoxin (lipopolysaccharide) and Staphylococcus aureus stimulation compared with human monocytes. Eur J Cell Biol 59(2):458–463Google Scholar
  160. Walker CM (1997) Comparative features of hepatitis C virus infection in humans and chimpanzees. Springer Semin Immunopathol 19(1):85–98PubMedGoogle Scholar
  161. Walsh GP, Tan EV, Dela Cruz EC, Abalos RM, Villahermosa LG, Young LJ, Cellona RV, Nazareno JB, Horwitz MA (1996) The Philippine cynomolgus monkey (Macaca fasicularis) provides a new nonhuman primate model of tuberculosis that resembles human disease. Nat Med 2(4):430–436PubMedGoogle Scholar
  162. Walsh DS, Dela Cruz EC, Abalos RM, Tan EV, Walsh GP, Portaels F, Meyers WM (2007) Clinical and histologic features of skin lesions in a cynomolgus monkey experimentally infected with mycobacterium ulcerans (Buruli ulcer) by intradermal inoculation. Am J Trop Med Hyg 76(1):132–134PubMedGoogle Scholar
  163. Werner H, Janitschke K, Kohler H (1969) Observations on marmoset monkeys of the species Saguinus (Oedipomidas) oedipus following oral and intraperitoneal infection by different cyst-forming Toxoplasma strains of varying virulence. I. Clinical, pathological anatomical and parasitological findings. Zentralbl Bakteriol Orig 209(4):553–569PubMedGoogle Scholar
  164. World Health Organization (2004) Manual for the monitoring of yellow fever virus infection. Immunization VaB Geneva, World Health Organization, Switzerland, p 68Google Scholar
  165. Wlasiuk G, Nachman MW (2010a) Adaptation and constraint at Toll-like receptors in primates. Mol Biol Evol 27(9):2172–2186PubMedCentralPubMedGoogle Scholar
  166. Wlasiuk G, Nachman MW (2010b) Promiscuity and the rate of molecular evolution at primate immunity genes. Evolution 64(8):2204–2220PubMedCentralPubMedGoogle Scholar
  167. Wlasiuk G, Khan S, Switzer WM, Nachman MW (2009) A history of recurrent positive selection at the Toll-like receptor 5 in primates. Mol Biol Evol 26(4):937–949PubMedCentralPubMedGoogle Scholar
  168. Woodall JP (1968) The reaction of a mangabey monkey (Cercocebus galeritus agilis Milne-Edwards) to inoculation with yellow fever virus. Ann Trop Med Parasitol 62(4):522–527PubMedGoogle Scholar
  169. Yang Z (2007) PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24(8): 1586–1591PubMedGoogle Scholar
  170. Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, Hieny S, Sutterwala FS, Flavell RA, Ghosh S et al (2005) TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308(5728):1626–1629PubMedGoogle Scholar
  171. Yim JJ, Ding L, Schaffer AA, Park GY, Shim YS, Holland SM (2004) A microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene: functional implications and racial differences. FEMS Immunol Med Microbiol 40(2):163–169PubMedGoogle Scholar
  172. Zahringer U, Lindner B, Inamura S, Heine H, Alexander C (2008) TLR2 - promiscuous or specific? A critical re-evaluation of a receptor expressing apparent broad specificity. Immunobiology 213(3–4):205–224PubMedGoogle Scholar
  173. Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, Segal D, Sancho-Shimizu V, Lorenzo L, Puel A et al (2007) TLR3 deficiency in patients with herpes simplex encephalitis. Science 317(5844):1522–1527PubMedGoogle Scholar
  174. Zhu J, Krishnegowda G, Li G, Gowda DC (2011) Proinflammatory responses by glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum are mainly mediated through the recognition of TLR2/TLR1. Exp Parasitol 128(3):205–211PubMedCentralPubMedGoogle Scholar
  175. Zurovsky Y, Laburn H, Mitchell D, MacPhail AP (1987) Responses of baboons to traditionally pyrogenic agents. Can J Physiol Pharmacol 65(6):1402–1407PubMedGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Pediatrics, CHU Sainte-Justine Research CenterUniversity of MontrealMontrealCanada
  2. 2.Department of AnthropologyUniversity of OregonEugeneUSA

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