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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2010, Vol. 4 Issue (4) : 385-393
Research articles
Toll-like receptors in innate immunity and infectious diseases
Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China;Department of Microbiology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou 510080, China;
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Abstract The protective ability of host defense system is largely dependent on germ-line encoded pattern-recognition receptors (PRRs). These PRRs respond to a variety of exogenous pathogens or endogenous danger signals, by recognizing some highly conserved structures such as pathogen-associated molecular patterns (PAMPs) and danger/damage associated molecular patterns (DAMPs). The most studied PRRs are Toll-like receptors (TLRs). Activation of TLRs triggers production of inflammatory cytokines and type I interferons (IFNs) via myeloid differentiation primary response gene 88 (MyD88)-dependent or-independent signaling respectively, thereby modulating innate and adaptive immunity, as well as inflammatory responses. This review introduces the classification, structure, and specific ligands of TLRs, and focuses on their signal pathways and biological activities, as well as clinical relevance. These studies of TLRs in the innate immune system have implications for the prevention and treatment of a variety of infectious diseases, including tuberculosis (TB), microbial keratitis, and hepatitis B and C.
Keywords Toll-like receptors      innate immunity      infectious disease      inflammation      
Issue Date: 05 December 2010
 Cite this article:   
Min-Hao WU,Xi HUANG,Ping ZHANG. Toll-like receptors in innate immunity and infectious diseases[J]. Front. Med., 2010, 4(4): 385-393.
Medzhitov R, Janeway C Jr. Innate immunity. N Engl J Med, 2000, 343(5): 338–344
PMID: 10922424
Janeway C A Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol, 2002, 20: 197–216
PMID: 11861602
Medzhitov R, Janeway C A Jr. How does the immune system distinguish self from nonself? Semin Immunol, 2000, 12(3): 185–188, discussion 257–344
PMID: 10910738
Foell D, Wittkowski H, Roth J. Mechanisms of disease: a "DAMP" view of inflammatory arthritis. Nat Clin Pract Rheumatol, 2007, 3(7): 382–390
PMID: 17599072
Fraser I P, Koziel H, Ezekowitz R A. The serum mannose-bindingprotein and the macrophage mannose receptor are pattern recognitionmolecules that link innate and adaptive immunity. Semin Immunol, 1998, 10(5): 363–372
PMID: 9799711
Bowdish D M, Gordon S. Conserved domains of the class A scavenger receptors: evolution and function. Immunol Rev, 2009, 227(1): 19–31
PMID: 19120472
Beutler B. Inferences, questions and possibilities in Toll-likereceptor signalling. Nature, 2004, 430(6996): 257–263
PMID: 15241424
Bianchi M E. DAMPs, PAMPs and alarmins: all we need to know aboutdanger. J Leukoc Biol, 2007, 81(1): 1–5
PMID: 17032697
Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol, 2004, 4(7): 499–511
PMID: 15229469
Wheeler D S, Chase M A, Senft A P, Poynter S E, Wong H R, Page K. Extracellular Hsp72, an endogenous DAMP, is releasedby virally infected airway epithelial cells and activates neutrophilsvia Toll-like receptor (TLR)-4. Respir Res, 2009, 10: 31
PMID: 19405961
Halayko A J, Ghavami S. S100A8/A9: a mediator of severe asthma pathogenesis and morbidity? Can J Physiol Pharmacol, 2009, 87(10): 743–755
PMID: 19898558
Jin M S, Lee J O. Structures of the toll-like receptor family and its ligand complexes. Immunity, 2008, 29(2): 182–191
PMID: 18701082
O'Neill L A, Bowie A G. The family of five: TIR-domain-containing adaptors in Toll-like receptorsignalling. Nat Rev Immunol, 2007, 7(5): 353–364
PMID: 17457343
Dowling D, Hamilton C M, O'Neill S M. A comparative analysis of cytokine responses, cell surface marker expression and MAPKs in DCsmatured with LPS compared with a panel of TLR ligands. Cytokine, 2008, 41(3): 254–262
PMID: 18221884
Lien E, Chow J C, Hawkins L D, McGuinness P D, Miyake K, Espevik T, Gusovsky F, Golenbock D T. A novel synthetic acycliclipid A-like agonist activates cells via the lipopolysaccharide/toll-likereceptor 4 signaling pathway. J Biol Chem, 2001, 276(3): 1873–1880
PMID: 11032843
Wang D, Lou J, Ouyang C, Chen W, Liu Y, Liu X, Cao X, Wang J, Lu L. Ras-related protein Rab10 facilitates TLR4 signaling by promotingreplenishment of TLR4 onto the plasma membrane. Proc Natl Acad Sci U S A, 2010, 107(31): 13806–13811
PMID: 20643919
Lang L L, Wang L, Liu L. Exogenous MD-2 Confers LipopolysaccharideResponsiveness to Human Corneal Epithelial Cells with IntracellularExpression of TLR4 and CD14. Inflammation 2010 Aug 11. doi: 10:1007/s10753-010-9244-x.

doi: 10:1007/s10753-010-9244-x
Aliprantis A O, Yang R B, Mark M R, Suggett S, Devaux B, Radolf J D, Klimpel G R, Godowski P, Zychlinsky A. Cell activation and apoptosis by bacterial lipoproteinsthrough toll-like receptor-2. Science, 1999, 285(5428): 736–739
PMID: 10426996
Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning C J. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediatedby toll-like receptor 2. J Biol Chem, 1999, 274(25): 17406–17409
PMID: 10364168
Takeda K, Takeuchi O, Akira S. Recognition of lipopeptidesby Toll-like receptors. J Endotoxin Res, 2002, 8(6): 459–463
PMID: 12697090
Ozinsky A, Underhill D M, Fontenot J D, Hajjar A M, Smith K D, Wilson C B, Schroeder L, Aderem A. The repertoire for patternrecognition of pathogens by the innate immune system is defined bycooperation between toll-like receptors. Proc Natl Acad Sci U S A, 2000, 97(25): 13766–13771
PMID: 11095740
Nakao Y, Funami K, Kikkawa S, Taniguchi M, Nishiguchi M, Fukumori Y, Seya T, Matsumoto M. Surface-expressed TLR6 participates in the recognition of diacylated lipopeptide and peptidoglycan in humancells. J Immunol, 2005, 174(3): 1566–1573
PMID: 15661917
Henneke P, Morath S, Uematsu S, Weichert S, Pfitzenmaier M, Takeuchi O, Müller A, Poyart C, Akira S, Berner R, Teti G, Geyer A, Hartung T, Trieu-Cuot P, Kasper D L, Golenbock D T. Role of lipoteichoic acidin the phagocyte response to group B streptococcus. J Immunol, 2005, 174(10): 6449–6455
PMID: 15879147
von Aulock S, Morath S, Hareng L, Knapp S, van Kessel K P, van Strijp J A, Hartung T. Lipoteichoic acid from Staphylococcus aureus is a potent stimulusfor neutrophil recruitment. Immunobiology, 2003, 208(4): 413–422
PMID: 14748514
Shimizu T, Kida Y, Kuwano K. A triacylated lipoprotein from Mycoplasmagenitalium activates NF-kappaB through Toll-like receptor 1 (TLR1)and TLR2. Infect Immun, 2008, 76(8): 3672–3678
PMID: 18474641
Shimizu T, Kida Y, Kuwano K. Triacylated lipoproteins derived fromMycoplasma pneumoniae activate nuclear factor-kappaB through toll-likereceptors 1 and 2. Immunology, 2007, 121(4): 473–483
PMID: 17433078
Hayashi F, Smith K D, Ozinsky A, Hawn T R, Yi E C, Goodlett D R, Eng J K, Akira S, Underhill D M, Aderem A. The innate immune responseto bacterial flagellin is mediated by Toll-like receptor 5. Nature, 2001, 410(6832): 1099–1103
PMID: 11323673
Yarovinsky F, Zhang D, Andersen J F, Bannenberg G L, Serhan C N, Hayden M S, Hieny S, Sutterwala F S, Flavell R A, Ghosh S, Sher A. TLR11 activation of dendritic cells bya protozoan profilin-like protein. Science, 2005, 308(5728): 1626–1629
PMID: 15860593
Zhang D, Zhang G, Hayden M S, Greenblatt M B, Bussey C, Flavell R A, Ghosh S. A toll-like receptor that prevents infection by uropathogenic bacteria. Science, 2004, 303(5663): 1522–1526
PMID: 15001781
Liu L, Botos I, Wang Y, Leonard J N, Shiloach J, Segal D M, Davies D R. Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science, 2008, 320(5874): 379–381
PMID: 18420935
Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S A. A Toll-like receptor recognizes bacterialDNA. Nature, 2000, 408(6813): 740–745
PMID: 11130078
Gantier M P, Tong S, Behlke M A, Xu D, Phipps S, Foster P S, Williams B R. TLR7 is involved in sequence-specific sensing of single-strandedRNAs in human macrophages. J Immunol, 2008, 180(4): 2117–2124
PMID: 18250417
Hammadi A, Billard C, Faussat A M, Kolb J P. Stimulation of iNOS expression and apoptosis resistancein B-cell chronic lymphocytic leukemia (B-CLL) cells through engagementof Toll-like receptor 7 (TLR-7) and NF-kappaB activation. Nitric Oxide, 2008, 19(2): 138–145
PMID: 18474259
Pivarcsi A, Nagy I, Koreck A, Kis K, Kenderessy-Szabo A, Szell M, Dobozy A, Kemeny L. Microbial compounds induce the expressionof pro-inflammatory cytokines, chemokines and human beta-defensin-2in vaginal epithelial cells. Microbes Infect, 2005, 7(9–10): 1117–1127
PMID: 15893496
Becker M N, Diamond G, Verghese M W, Randell S H. CD14-dependent lipopolysaccharide-induced beta-defensin-2expression in human tracheobronchial epithelium. J Biol Chem, 2000, 275(38): 29731–29736
PMID: 10882713
Alter G, Suscovich T J, Teigen N, Meier A, Streeck H, Brander C, Altfeld M. Single-stranded RNA derived from HIV-1 serves as a potentactivator of NK cells. J Immunol, 2007, 178(12): 7658–7666
PMID: 17548602
Wang J, Shao Y, Bennett T A, Shankar R A, Wightman P D, Reddy L G. The functional effects of physical interactions amongToll-like receptors 7, 8, and 9. J Biol Chem, 2006, 281(49): 37427–37434
PMID: 17040905
Yarovinsky F, Sher A. Toll-like receptor recognition of Toxoplasma gondii. Int J Parasitol, 2006, 36(3): 255–259
PMID: 16476433
Hasan U, Chaffois C, Gaillard C, Saulnier V, Merck E, Tancredi S, Guiet C, Brière F, Vlach J, Lebecque S, Trinchieri G, Bates E E. Human TLR10 is a functional receptor, expressed by Bcells and plasmacytoid dendritic cells, which activates gene transcriptionthrough MyD88. J Immunol, 2005, 174(5): 2942–2950
PMID: 15728506
Guan Y, Ranoa D R, Jiang S, Mutha S K, Li X, Baudry J, Tapping R I. Human TLRs 10 and 1 share common mechanisms of innate immune sensingbut not signaling. J Immunol, 2010, 184(9): 5094–5103
PMID: 20348427
Schnare M, Barton G M, Holt A C, Takeda K, Akira S, Medzhitov R. Toll-like receptors control activation of adaptive immuneresponses. Nat Immunol, 2001, 2(10): 947–950
PMID: 11547333
Vora P, Youdim A, Thomas L S, Fukata M, Tesfay S Y, Lukasek K, Michelsen K S, Wada A, Hirayama T, Arditi M, Abreu M T. Beta-defensin-2 expression is regulatedby TLR signaling in intestinal epithelial cells. J Immunol, 2004, 173(9): 5398–5405
PMID: 15494486
Wu M, McClellan S A, Barrett R P, Hazlett L D. Beta-defensin-2 promotes resistance against infectionwith P. aeruginosa. J Immunol, 2009, 182(3): 1609–1616
PMID: 19155510
Wu M, McClellan S A, Barrett R P, Zhang Y, Hazlett L D. Beta-defensins 2 and 3 together promote resistance to Pseudomonasaeruginosa keratitis. J Immunol, 2009, 183(12): 8054–8060
PMID: 19933858
Chen X M, O'Hara S P, Nelson J B, Splinter P L, Small A J, Tietz P S, Limper A H, LaRusso N F. Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responsesto Cryptosporidium parvum via activation of NF-kappaB. J Immunol, 2005, 175(11): 7447–7456
PMID: 16301652
Kumar A, Yin J, Zhang J, Yu F S. Modulation of corneal epithelial innate immune response to pseudomonasinfection by flagellin pretreatment. Invest Ophthalmol Vis Sci, 2007, 48(10): 4664–4670
PMID: 17898290
Funderburg N, Lederman M M, Feng Z, Drage M G, Jadlowsky J, Harding C V, Weinberg A, Sieg S F. Human-defensin-3 activates professional antigen-presenting cells via Toll-like receptors1 and 2. Proc Natl Acad Sci U S A, 2007, 104(47): 18631–18635
PMID: 18006661
Biragyn A, Ruffini P A, Leifer C A, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa A K, Farber J M, Segal D M, Oppenheim J J, Kwak L W. Toll-like receptor 4-dependentactivation of dendritic cells by beta-defensin 2. Science, 2002, 298(5595): 1025–1029
PMID: 12411706
Davila S, Hibberd M L, Hari Dass R, Wong H E, Sahiratmadja E, Bonnard C, Alisjahbana B, Szeszko J S, Balabanova Y, Drobniewski F, van Crevel R, van de Vosse E, Nejentsev S, Ottenhoff T H, Seielstad M. Genetic association and expressionstudies indicate a role of toll-like receptor 8 in pulmonary tuberculosis. PLoS Genet, 2008, 4(10): e1000218
PMID: 18927625
Ma X, Liu Y, Gowen B B, Graviss E A, Clark A G, Musser J M. Full-exon resequencing reveals toll-like receptor variantscontribute to human susceptibility to tuberculosis disease. PLoS One, 2007, 2(12): e1318
PMID: 18091991
Velez D R, Wejse C, Stryjewski M E, Abbate E, Hulme W F, Myers J L, Estevan R, Patillo S G, Olesen R, Tacconelli A, Sirugo G, Gilbert J R, Hamilton C D, Scott W K. Variants in toll-like receptors2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians,African-Americans, and West Africans. Hum Genet, 2010, 127(1): 65–73
PMID: 19771452
Abel B, Thieblemont N, Quesniaux V J, Brown N, Mpagi J, Miyake K, Bihl F, Ryffel B. Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infectionin mice. J Immunol, 2002, 169(6): 3155–3162
PMID: 12218133
Yang C S, Shin D M, Lee H M, Son J W, Lee S J, Akira S, Gougerot-Pocidalo M A, El-Benna J, Ichijo H, Jo E K. ASK1-p38 MAPK-p47phox activation is essential for inflammatory responses duringtuberculosis via TLR2-ROS signalling. Cell Microbiol, 2008, 10(3): 741–754
PMID: 18028450
Castiblanco J, Varela D C, Casta?o-Rodríguez N, Rojas-Villarraga A, Hincapié M E, Anaya J M. TIRAP (MAL) S180L polymorphism is a common protective factor againstdeveloping tuberculosis and systemic lupus erythematosus. Infect Genet Evol, 2008, 8(5): 541–544
PMID: 18417424
Dissanayeke S R, Levin S, Pienaar S, Wood K, Eley B, Beatty D, Henderson H, Anderson S, Levin M. Polymorphic variation in TIRAP is not associated withsusceptibility to childhood TB but may determine susceptibility toTBM in some ethnic groups. PLoS One, 2009, 4(8): e6698
PMID: 19693265
Doherty T M, Arditi M T B. TB, or not TB: that is the question — does TLR signaling hold the answer? J Clin Invest, 2004, 114(12): 1699–1703
PMID: 15599394
Hazlett L D. Corneal response to Pseudomonas aeruginosa infection. Prog Retin Eye Res, 2004, 23(1): 1–30
PMID: 14766315
Jin X, Lin Z, Xie X. The delayed response of Toll-like receptorsmay relate to Pseudomonas aeruginosa keratitis exacerbating rapidlyat the early stages of infection. Eur J Clin Microbiol Infect Dis, 2010, 29(2): 231–238
PMID: 20012880
Gao N, Kumar A, Jyot J, Yu F S. Flagellin-induced corneal antimicrobial peptide production and woundrepair involve a novel NF-kappaB-independent and EGFR-dependent pathway. PLoS One, 2010, 5(2): e9351
PMID: 20195469
Hazlett L D, McClellan S, Kwon B, Barrett R. Increased severity of Pseudomonas aeruginosa cornealinfection in strains of mice designated as Th1 versus Th2 responsive. Invest Ophthalmol Vis Sci, 2000, 41(3): 805–810
PMID: 10711697
Huang X, Barrett R P, McClellan S A, Hazlett L D. Silencing Toll-like receptor-9 in Pseudomonas aeruginosakeratitis. Invest Ophthalmol Vis Sci, 2005, 46(11): 4209–4216
PMID: 16249500
Huang X, Du W, McClellan S A, Barrett R P, Hazlett L D. TLR4 is required for host resistance in Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci, 2006, 47(11): 4910–4916
PMID: 17065506
Huang X, Hazlett L D, Du W, Barrett R P. SIGIRR promotes resistance against Pseudomonas aeruginosakeratitis by down-regulating type-1 immunity and IL-1R1 and TLR4 signaling. J Immunol, 2006, 177(1): 548–556
PMID: 16785552
Huang X, Du W, Barrett R P, Hazlett L D. ST2 is essential for Th2 responsiveness and resistance to pseudomonasaeruginosa keratitis. Invest OphthalmolVis Sci, 2007, 48(10): 4626–4633
PMID: 17898286
Lok A S, McMahon B J, 0. Chronic hepatitis B. Hepatology, 2001, 34(6): 1225–1241
PMID: 11732013
Rantala M, van de Laar M J. Surveillance and epidemiology of hepatitis B and C in Europe- a review. Euro Surveill, 2008, 13(21): 13
PMID: 18761967
Brown R A, Gralewski J H, Eid A J, Knoll B M, Finberg R W, Razonable R R. R753Q single-nucleotide polymorphism impairs toll-like receptor 2 recognition of hepatitis C virus coreand nonstructural 3 proteins. Transplantation, 2010, 89(7): 811–815
PMID: 20090572
Li Y, Chang M, Abar O, Garcia V, Rowland C, Catanese J, Ross D, Broder S, Shiffman M, Cheung R, Wright T, Friedman S L, Sninsky J. Multiple variants in toll-likereceptor 4 gene modulate risk of liver fibrosis in Caucasians withchronic hepatitis C infection. J Hepatol, 2009, 51(4): 750–757
PMID: 19586676
Askar E, Bregadze R, Mertens J, Schweyer S, Rosenberger A, Ramadori G, Mihm S. TLR3 gene polymorphisms and liver disease manifestationsin chronic hepatitis C. J Med Virol, 2009, 81(7): 1204–1211
PMID: 19475618
Schott E, Witt H, Neumann K, Taube S, Oh D Y, Schreier E, Vierich S, Puhl G, Bergk A, Halangk J, Weich V, Wiedenmann B, Berg T A. A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammationand fibrosis in male patients with chronic HCV-infection. J Hepatol, 2007, 47(2): 203–211
PMID: 17512627
Zhou J, Huang Y, Tian D, Xu D, Chen M, Wu H. Expression of toll-like receptor 9 in peripheral bloodmononuclear cells from patients with different hepatitis B and C viralloads. J Huazhong Univ Sci Technolog MedSci, 2009, 29(3): 313–317
PMID: 19513613
Wang J P, Zhang Y, Wei X, Li J, Nan X P, Yu H T, Li Y, Wang P Z, Bai X F. Circulating Toll-like receptor (TLR) 2, TLR4, and regulatory T cellsin patients with chronic hepatitis C. APMIS, 2010, 118(4): 261–270
PMID: 20402671
Lester R T, Yao X D, Ball T B, McKinnon L R, Kaul R, Wachihi C, Jaoko W, Plummer F A, Rosenthal K L. Toll-like receptor expression and responsiveness are increased inviraemic HIV-1 infection. AIDS, 2008, 22(6): 685–694
PMID: 18356597
Ahmed N, Hayashi T, Hasegawa A, Furukawa H, Okamura N, Chida T, Masuda T, Kannagi M. Suppression of human immunodeficiency virus type-1 (HIV-1) replication in macrophagesby commensal bacteria preferentially stimulating toll-like receptor4. J Gen Virol2010, 91(Pt 11): 2804–2813.
Pine S O, McElrath M J, Bochud P Y. Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincidentcohort of HIV-1-infected individuals. AIDS, 2009, 23(18): 2387–2395
PMID: 19855253
Báfica A, Scanga C A, Schito M, Chaussabel D, Sher A. Influence of coinfectingpathogens on HIV expression: evidence for a role of Toll-like receptors. J Immunol, 2004, 172(12): 7229–7234
PMID: 15187096
Bochud P Y, Hersberger M, Taffé P, Bochud M, Stein C M, Rodrigues S D, Calandra T, Francioli P, Telenti A, Speck R F, Aderem A, 0. Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection. AIDS, 2007, 21(4): 441–446
PMID: 17301562
Soriano-Sarabia N, Vallejo A, Ramírez-Lorca R, Rodríguez Mdel M, Salinas A, Pulido I, Sáez M E, Leal M. Influence of the Toll-like receptor 9 1635A/G polymorphismon the CD4 count, HIV viral load, and clinical progression. J Acquir Immune Defic Syndr, 2008, 49(2): 128–135
PMID: 18769358
Guillot L, Le Goffic R, Bloch S, Escriou N, Akira S, Chignard M, Si-Tahar M. Involvement of toll-like receptor 3 in the immune response of lungepithelial cells to double-stranded RNA and influenza A virus. J Biol Chem, 2005, 280(7): 5571–5580
PMID: 15579900
Marshall-Clarke S, Tasker L, Buchatska O, Downes J, Pennock J, Wharton S, Borrow P, Wiseman D Z. Influenza H2 haemagglutinin activates B cells via a MyD88-dependentpathway. Eur J Immunol, 2006, 36(1): 95–106
PMID: 16323245
Wang J P, Bowen G N, Padden C, Cerny A, Finberg R W, Newburger P E, Kurt-Jones E A. Toll-like receptor-mediated activation of neutrophils by influenzaA virus. Blood, 2008, 112(5): 2028–2034
PMID: 18544685
Pierik M, Joossens S, Van Steen K, Van Schuerbeek N, Vlietinck R, Rutgeerts P, Vermeire S. Toll-like receptor-1, -2, and-6 polymorphisms influencedisease extension in inflammatory bowel diseases. Inflamm Bowel Dis, 2006, 12(1): 1–8
T?r?k H P, Glas J, Endres I, Tonenchi L, Teshome M Y, Wetzke M, Klein W, Lohse P, Ochsenkühn T, Folwaczny M, G?ke B, Folwaczny C, Müller-Myhsok B, Brand S. Epistasis between Toll-like receptor-9 polymorphisms and variantsin NOD2 and IL23R modulates susceptibility to Crohn's disease. Am J Gastroenterol, 2009, 104(7): 1723–1733
PMID: 19455129
Franchimont D, Vermeire S, El Housni H, Pierik M, Van Steen K, Gustot T, Quertinmont E, Abramowicz M, Van Gossum A, Devière J, Rutgeerts P. Deficient host-bacteria interactions in inflammatory bowel disease?The toll-like receptor (TLR)-4 Asp299gly polymorphism is associatedwith Crohn's disease and ulcerative colitis. Gut, 2004, 53(7): 987–992
PMID: 15194649
Gewirtz A T, Vijay-Kumar M, Brant S R, Duerr R H, Nicolae D L, Cho J H. Dominant-negative TLR5 polymorphismreduces adaptive immune response to flagellin and negatively associateswith Crohn's disease. Am J PhysiolGastrointest Liver Physiol, 2006, 290(6): G1157–G1163
PMID: 16439468
Leoratti F M, Farias L, Alves F P, Suarez-Mútis M C, Coura J R, Kalil J, Camargo E P, Moraes S L, Ramasawmy R. Variants in the toll-like receptor signaling pathwayand clinical outcomes of malaria. J Infect Dis, 2008, 198(5): 772–780
PMID: 18662133
Hamann L, Bedu-Addo G, Eggelte T A, Schumann R R, Mockenhaupt F P. The toll-like receptor 1 variant S248N influences placental malaria. Infect Genet Evol, 2010, 10(6): 785–789
PMID: 20478407
Basu M, Maji A K, Chakraborty A, Banerjee R, Mullick S, Saha P, Das S, Kanjilal S D, Sengupta S. Genetic association of Toll-like-receptor4 and tumor necrosis factor-alpha polymorphisms with Plasmodium falciparumblood infection levels. Infect Genet Evol, 2010, 10(5): 686–696
PMID: 20307689
Chen J, Xu W, Zhou T, Ding Y, Duan J, Huang F. Inhibitory role of toll-like receptors agonists in Plasmodiumyoelii liver stage development. Parasite Immunol, 2009, 31(8): 466–473
PMID: 19646211
Greene J A, Moormann A M, Vulule J, Bockarie M J, Zimmerman P A, Kazura J W. Toll-like receptor polymorphisms in malaria-endemicpopulations. Malar J, 2009, 8: 50
PMID: 19317913
Crompton P D, Mircetic M, Weiss G, Baughman A, Huang C Y, Topham D J, Treanor J J, Sanz I, Lee F E, Durbin A P, Miura K, Narum D L, Ellis R D, Malkin E, Mullen G E, Miller L H, Martin L B, Pierce S K. The TLR9 ligand CpG promotesthe acquisition of Plasmodium falciparum-specific memory B cells inmalaria-naive individuals. J Immunol, 2009, 182(5): 3318–3326
PMID: 19234231
Sam-Agudu N A, Greene J A, Opoka R O, Kazura J W, Boivin M J, Zimmerman P A, Riedesel M A, Bergemann T L, Schimmenti L A, John C C. TLR9 polymorphismsare associated with altered IFN-gamma levels in children with cerebralmalaria. Am J Trop Med Hyg, 2010, 82(4): 548–555
PMID: 20348497
Wong S H, Gochhait S, Malhotra D, Pettersson F H, Teo Y Y, Khor C C, Rautanen A, Chapman S J, Mills T C, Srivastava A, Rudko A, Freidin M B, Puzyrev V P, Ali S, Aggarwal S, Chopra R, Reddy B S, Garg V K, Roy S, Meisner S, Hazra S K, Saha B, Floyd S, Keating B J, Kim C, Fairfax B P, Knight J C, Hill P C, Adegbola R A, Hakonarson H, Fine P E, Pitchappan R M, Bamezai R N, Hill A V, Vannberg F O. Leprosy and the adaptation of human toll-like receptor 1. PLoS Pathog, 2010, 6: e1000979
PMID: 20617178
Schuring R P, Hamann L, Faber W R, Pahan D, Richardus J H, Schumann R R, Oskam L. Polymorphism N248S in the human Toll-like receptor 1 gene is related to leprosyand leprosy reactions. J Infect Dis, 2009, 199(12): 1816–1819
PMID: 19456232
Krutzik S R, Ochoa M T, Sieling P A, Uematsu S, Ng Y W, Legaspi A, Liu P T, Cole S T, Godowski P J, Maeda Y, Sarno E N, Norgard M V, Brennan P J, Akira S, Rea T H, Modlin R L. Activation and regulation of Toll-likereceptors 2 and 1 in human leprosy. Nat Med, 2003, 9(5): 525–532
PMID: 12692544
Johnson C M, Lyle E A, Omueti K O, Stepensky V A, Yegin O, Alpsoy E, Hamann L, Schumann R R, Tapping R I. Cutting edge: A common polymorphism impairs cell surfacetrafficking and functional responses of TLR1 but protects againstleprosy. J Immunol, 2007, 178(12): 7520–7524
PMID: 17548585
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