A invasão de patógenos no hospedeiro pode ser controlada e resolvida pelo sistema imune inato, entretanto na maioria das situações infecciosas, respostas imunes adaptativas são requeridas para controlar ou debelar o processo infeccioso (IWASAKI; MEDZHITOV, 2004).
A ligação dos TLR das APCs com seus ligantes direciona a regulação positiva do MHC e de moléculas coestimulatórias que são capazes de fornecer os sinais essenciais para a ativação das células T naïve (MEDZHITOV, 2001; MIYAJI et al., 2011). Além disso, a modulação do sistema imune adaptativo necessita da apresentação de antígenos por APCs, e das citocinas que são importantes para a expansão clonal de suas células efetoras. Portanto a ligação de PAMPs e DAMPs aos RRPs é uma etapa essencial para as respostas imunes adaptativas (WALLIN et al., 2002).
A apresentação de antígenos por APCs as células T, resulta na expansão clonal e ativação dessas células. Existem dois tipos de células T, as células T CD8+ que são células citotóxicas capazes de destruir diretamente células infectadas, e células T CD4 + que são células com distintos fenótipos, com funções celulares (ativação de macrófagos) e humorais (ativação de linfócitos B) (MOSER; LEO, 2010).
REFERÊNCIAS
ADEREM, A.; ULEVITCH, R. J. Toll-like receptors in the induction of the innate immune response. Nature, London, v. 406, n. 6797, p. 782-787, 2000. AKIRA, S. et al. Pathogen recognition and innate immunity. Cell, Cambridge, v. 24, p. 783-801, 2006.
AKIRA, S.; TAKEDA, K.; KAISHO, T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nature Immunology, New York, v. 2, n. 8, p. 675-680, 2001.
ALCAIDE, M.; EDWARDS, S. V. Molecular evolution of the toll-like receptor multigene family in birds. Molecular Biology and Evolution, Chicago, v. 28, n. 5, p. 1703-1715, 2011.
ANDERSON, K. V. Toll signaling pathways in the innate immune response. Current Opinion in Immunology, London, v. 12, n. 1, p. 13-19, 2000.
ARBOUR, N. C. et al. TLR4 mutations are associated with endotoxin
hyporesponsiveness in humans. Nature Genetics, New York, v. 25, n. 2, p. 187- 190, 2000.
ASEA, A. et al. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. Journal of Biological Chemistry, Baltimore, v. 277, n. 17, p. 15028-15034, 2002.
AUCOUTURIER, J.; DUPUIS, L.; GANNE, V. Adjuvants designed for veterinary and human vaccines. Vaccine, Kidlinton, v. 19, n. 17/19, p. 2666- 2672, 2001.
BABIUK, L. A. Vaccination: a management tool in veterinary medicine. Veterinary Journal, London, v. 164, n. 3, p. 188-201, 2002.
BASU, S. et al. DC91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity, Cambridge, v. 14, n. 3, p. 303-113, Mar. 2001.
BAUER, S. et al. Human TLR9 confers responsiveness to bacterial DNA via species: specific CpG motif recognition. Nature, London, v. 98, p. 9237-9242, 2001.
BERIN, M. C. et al. Role of EHEC O157: H7 virulence factors in the activation of intestinal epithelial cell NF-kappa B and MAP kinase pathways and the upregulated expression of interleukin 8. Cellular Microbiology, Oxford, v. 4, n. 10, p. 635-648, Oct. 2002.
BEUTLER, B. Innate immunity: an overview. Molecular Immunology, Elmsford, v. 40, n. 12, p. 845-859, Feb. 2004.
BIANCHI, M. E. DAMPs, PAMPs and alarmins: all we need to know about danger. Journal of Leukocyte Biology, New York, v. 81, n. 1, p. 1-5, Jan. 2007. BONIFIELD, H. R.; HUGHES, K. T. Flagellar phase variation in Salmonella enterica is mediated by a posttranscriptional control mechanism. Journal of Bacteriology, Washington, v. 185, n. 12, p. 3567-3574, 2003.
BOYD, Y. et al. Mapping of chicken and mouse genes for Toll-like receptor 2 (TLR2) to an evolutionarily conserved chromosomal segment.
Immunogenetics, New York, v. 52, p. 294-298, 2001.
CHAUNG, H. C. et al. Salmonella flagellin enhances mucosal immunity of avian influenza vaccine in chickens. Veterinary Microbiology, Amsterdam, v. 157, n. 1/2, p. 69-77, 2012.
CUNNINGHAM, A. F. et al. Responses to the soluble flagellar protein FliC are Th2, while those to FliC on Salmonella are Th1. European Journal of
Immunology, Weinheim, v. 34, n. 11, p. 2986-2995, Nov. 2004.
DALPKE, A.; HEEG, K. Signal integration following toll-like receptor triggering. Critical Reviews in Immunology, Boca Raton, v. 22, n. 3, p. 217- 250, 2002.
DIDIERLAURENT, A. et al. Flagellin promotes myeloid differentiation factor 88-dependent development of Th2-type response. Journal of Immunology, Baltimore, v. 172, n. 11, p. 6922-6930, June 2004.
DIL, N.; QURESHI, M. A. Differential expression of inducible nitric oxide synthase is associated with differential Toll-like receptor-4 expression in chicken macrophages from different genetic backgrounds. Veterinary Immunology and Immunopathology, Amsterdam, v. 84, n. 3/4, p. 191-207, 2002.
DREXLER, S. K.; FOXWELL, B. M. The role of toll-like receptors in chronic inflammation. International Journal of Biochemistry & Cell Biology, Exeter, v. 42, n. 4, p. 506-518, Apr. 2010.
EAVES-PYLES, T. D. et al. Salmonella flagellin-dependent proinflammatory responses are localized to the conserved amino and carboxyl regions of the protein. Journal of Immunology, Baltimore, v. 167, n. 12, p. 7009-7016, Dec. 2001.
ERRIDGE, C. Endogenous ligands of TLR2 and TLR4: agonists or assistants? Journal of Leukocyte Biology, New York, v. 6, p. 989-999, 2010.
FARNELL, M. B. et al. Oxidative burst mediated by toll like receptors (TLR) and CD14 on avian heterophils stimulated with bacterial toll agonists.
Developmental and Comparative Immunology, New York, v. 27, n. 5, p. 423- 429, May 2003.
FRANCIS, A. E. The future of vaccines, immunization concepts and practice. Vaccine, Kidlinton, v. 19, p. 2206-2209, 2001.
FUKU, A. et al. Molecular cloning and functional characterization of chicken toll-like receptors: a single chicken toll covers multiple molecular patterns. Journal of Biological Chemistry, Baltimore, v. 276, n. 50, p. 47143-47149, Dec. 2001.
GENOVESE, K. J. et al. Dynamics of the avian inflammatory response to Salmonella following administration of the toll-like receptor 5 agonist flagellin. FEMS Immunology and Medical Microbiology, Amsterdam, v. 51, n. 1, p. 112-117, Oct. 2007.
GEWIRTZ, A. T. et al. Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. Journal of Clinical Investigation, Michigan, v. 107, n. 1, p. 99-109, Jan. 2001.
GOMIS, S. et al. Protection of neonatal chicks against a lethal challenge of Escherichia coli using DNA containing cytosine-phosphodiester-guanine motifs. Avian Diseases, Kennett Square, v. 48, n. 4, p. 813-822, Dec. 2004.
HAYASHI, F. et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature, London, v. 410, n. 6832, p. 1099- 1103, Apr. 2001.
HE, H. Q. et al. Identification of CpG oligodeoxynucleotide motifs that stimulate nitric oxide and cytokine production in avian macrophage and peripheral blood mononuclear cells. Developmental and Comparative Immunology, New York, v. 27, n. 6/7, p. 621-627, Jan./July 2003.
HULEATT, J. W. et al. Vaccination with recombinant fusion proteins incorporating Toll-like receptor ligands induces rapid cellular and humoral immunity. Vaccine, Kidlinton, v. 25, n. 4, p. 763-775, 2007.
HYBISKE, K. et al. Cystic fibrosis airway epithelial cell polarity and bacterial flagellin determine host response to Pseudomonas aeruginosa. Cellular Microbiology, Oxford, v. 6, n. 1, p. 49-63, Jan. 2004.
IQBAL, M. et al. Identification and functional characterization of chicken Toll- like receptor 5 reveals a fundamental role in the biology of infection with Salmonella enterica serovar typhimurium. Infection and Immunity, Washington, v. 73, n. 4, p. 2344-2350, Apr. 2005.
IWASAKI, A.; MEDZHITOV, R. Toll-like receptor control of the adaptive immune responses. Nature Immunology, New York, v. 5, n. 10, p. 987-995, Oct. 2004.
JANEWAY, C. A.; MEDZHITOV, R. Innate immune recognition. Annual Review of Immunology, Palo Alto, v. 20, p. 197-216, 2002.
JUUL-MADSEN, H. R. et al. Avian innate immune responses. In: DAVISON, F.; KASPERS, B.; SCHAT, K. A. (Ed.). Avian immunology. London: Academic, 2008. p. 129-158.
KAISER, P. Advances in avian immunology-prospects for disease control: a review. Avian Pathology, Huntindgon, v. 39, n. 5, p. 309-324, 2010.
______. The avian immune genome a glass half-full or half-empty? Cytogenetic and Genome Research, Würzburg, v. 117, n. 1/4, p. 221-230, 2007.
KAISER, P. et al. A genomic analysis of chicken cytokines and chemokines. Journal of Interferon & Cytokine Research, New Rochelle, v. 8, p. 467-484, 2005.
KARPALA, A. J.; LOWENTHAL, J. W.; BEAN, A. G. Activation of the TLR3 pathway regulates IFN beta production in chickens. Developmental and Comparative Immunology, New York, v. 32, n. 4, p. 435-444, Apr. 2008.
KAWAI, T.; AKIRA, S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity, Cambridge, v. 34, n. 5, p. 637- 650, 2011.
KEESTRA, A. M. et al. Functional characterization of chicken TLR5 reveals species-specific recognition of flagellin. Molecular Immunology, Elmsford, v. 45, n. 5, p. 1298-1307, Mar. 2008.
KOGUT, M. H. et al. Expression and function of Toll-like receptors in chicken heterophils. Developmental and Comparative Immunology, New York, v. 29, n. 9, p. 791-807, Sept. 2005.
______. In-vivo activation of heterophil function in chickens following injection with salmonella enteritidis-immune lymphokines. Journal of Leukocyte Biology, New York, v. 57, n. 1, p. 56-62, Jan. 1995.
KOGUT, M. H.; HE, H.; GENOVESE, K. J. Bacterial toll-like receptor agonists induce sequential NF-kappa B-mediated leukotriene B-4 and prostaglandin E-2 production in chicken heterophils. Veterinary Immunology and
Immunopathology, Amsterdam, v. 145, n. 1/2, p. 159-170, Jan. 2012.
KONO, H.; ROCK, K. L. How dying cells alert the immune system to danger. Nature Reviews Immunology, London, v. 8, n. 4, p. 279-289, 2008.
LEE, S. E. et al. A bacterial flagellin, Vibrio vulnificus FlaB, has a strong mucosal adjuvant activity to induce protective immunity. Infection and Immunity, Washington, v. 74, n. 1, p. 694-702, 2006.
LI, Z. H.; MENORET, A.; SRIVASTAVA, P. Roles of heat-shock proteins in antigen presentation and cross-presentation. Current Opinion in Immunology, London, v. 14, n. 1, p. 45-51, 2002.
LUONG, M. et al. Stimulation of TLR4 by recombinant HSP70 requires structural integrity of the HSP70 protein itself. Journal of Inflammation, New York, v. 9, n. 1, p. 11-16, Jan. 2012.
MACNAB, R. M. How bacteria assemble flagella. Annual Review of Microbiology, Palo Alto, v. 57, p. 77-100, May 2003.
MEANS, T. K.; GOLENBOCK, D. T.; FENTON, M. J. Structure and function of Toll-like receptor proteins. Life Sciences, Varsovia, v. 68, n. 3, p. 241-258, 2000.
MEDZHITOV, R. Toll-like receptors and innate immunity. Nature Reviews Immunology, London, v. 1, n. 2, p. 135-145, 2001.
METCALFE, H. J. et al. Flagellin expression enhances Salmonella accumulation in TLR5-positive macrophages. Developmental and
Comparative Immunology, New York, v. 34, n. 8, p. 797-804, Aug. 2010.
MIYAJI, E. N. et al. Trends in adjuvant development for vaccines: DAMPs and PAMPs as potential new adjuvants. Brazilian Journal of Medical and
Biological Research, Ribeirão Preto, v. 44, n. 6, p. 500-513, Dec. 2011.
MOSER, M.; LEO, O. Key concepts in immunology. Vaccine, Kidlinton, v. 28, n. 3, p. 2-13, 2010. Supplement.
MUZIO, M.; MANTOVANI, A. Toll-like receptors. Microbes and Infection, Paris, v. 2, n. 3, p. 251-255, 2000.
NEWTON, K.; DIXIT, V. M. Signaling in innate immunity and inflammation. Cold Spring Harbor Perspectives in Biology, New York, v. 4, n. 3, Mar. 2012. Disponível em: <http://cshperspectives.cshlp.org/content/4/3/a006049.full>. Acesso em: 10 dez. 2012.
NOESSNER, E. et al. Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. Journal of Immunology, Baltimore, v. 169, n. 10, p. 5424-5432, Oct. 2002.
OHASHI, K. et al. Heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. Journal of Immunology, Baltimore, v. 164, n. 2, p. 558-561, Feb. 2000.
O'NEILL, L. A. J. Signal transduction pathways activated by the IL-1
receptor/Toll-like receptor superfamily. Toll-Like Receptor Family Members and Their Ligands, Oxford, n. 270, p. 47-61, 2002.
PASARE, C.; MEDZHITOV, R. Toll-like receptors: linking innate and adaptive immunity. Microbes and Infection, Paris, v. 6, n. 15, p. 1382-1387, 2004. PAUL, M. S. et al. Prophylactic treatment with Toll-like receptor ligands enhances host immunity to avian influenza virus in chickens. Vaccine, Kidlinton, v. 30, n. 30, p. 4524-4531, 2012.
POCKLEY, A. G. Heat shock proteins in health and disease: therapeutic targets or therapeutic agents? Expert Reviews in Molecular Medicine, Trenton, v. 23, p. 1-21, 2001.
PUTTEN, J. P. M. van; BOUWMAN, L. I.; DE ZOETE, M. R. Unraveling bacterial interactions with Toll-like receptors. Immunology Letters, Amsterdam, v. 128, n. 1, p. 8-11, Jan. 2010.
RAMOS, H. C.; RUMBO, M.; SIRARD, J. C. Bacterial flagellins: mediators of pathogenicity and host immune responses in mucosa. Trends in Microbiology, Cambridge, v. 12, n. 11, 509-517, Nov. 2004.
RUAN, W.; WU, Y.; ZHENG, S. J. Different genetic patterns in avian Toll-like receptor (TLR) 5 genes. Molecular Biology Reports, Dordrecht, v. 39, n. 4, p. 3419-3426, Apr. 2011.
SKOUNTZOU, I. et al. Salmonella flagellins are potent adjuvants for intranasally administered whole inactivated influenza vaccine. Vaccine, Kidlinton, v. 28, n. 24, p. 4103-4112, May 2010.
SMITH, K. D. et al. Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nature
Immunology, New York, v. 5, n. 4, p. 1247-1251, Apr. 2004.
SOMERSAN, S. et al. Primary tumor tissue lysates are enriched in heat shock proteins and induce the maturation of human dendritic cells. Journal of Immunology, Baltimore, v. 167, n. 9, p. 4844-4852, Nov. 2001.
STEWART, G. R. et al. Overexpression of heat-shock proteins reduces survival of Mycobacterium tuberculosis in the chronic phase of infection. Nature Medicine, New York, v. 7, n. 6, p. 732-737, Dec. 2001.
STEWART, G. R.; YOUNG, D. B. Heat-shock proteins and the host-pathogen interaction during bacterial infection. Current Opinion in Immunology, London, v. 16, n. 4, p. 506-510, Apr. 2004.
SUZUKI, N. et al. Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature, London, v. 416, n. 6882, p. 750- 754, 2002.
TAKEUCHI, O.; AKIRA, S. Pattern recognition receptors and inflammation. Cell, Cambridge, v. 140, n. 6, p. 805-820, Mar. 2010.
TAPPING, R. I. Innate immune sensing and activation of cell surface Toll-like receptors. Seminars in Immunology, Philadelphia, v. 21, n. 4, p. 175-184, Aug. 2009.
TEMPERLEY, N. D. et al. Evolution of the chicken Toll-like receptor gene family: a story of gene gain and gene loss. BMC Genomics, London, v. 9, n. 62, p. 62-66, Feb. 2008.
TOBIAN, A. A. et al. Bacterial heat shock proteinspromote CD91-dependent class I MHC cross presentation of chaperoned peptide to CD8+ T cells by cytosolic mechanisms in dendritic cells versus vacuolar mechanisms in macrophages. Journal of Immunology, Baltimore, v. 172, n. 9, p. 5277-5286, May 2004.
TSAN, M. F.; GAO, B. Heat shock proteins and immune system. Journal of Leukocyte Biology, New York, v. 85, n. 6, p. 905-910, Dec. 2009.
UNIÃO BRASILEIRA DE AVICULTURA. Relatório anual: Ubabef. São Paulo, 2012. 57 p.
VABULAS, R. M. et al. HSP70 as endogenous stimulus of the toll/interleukin-1 receptor signal pathway. Journal of Biological Chemistry, Baltimore, v. 277, n. 17, p. 15107-15112, 2002.
VASSELON, T.; DETMERS, P. A. Toll receptors: a central element in innate immune responses. Infection and Immunity, Washington, v. 70, n. 3, p. 1033- 1041, 2002.
WALLIN, R. P. A. et al. Heat-shock proteins as activators of the innate immune system. Trends in Immunology, London, v. 23, n. 3, p. 130-135, 2002.
WERLING, D.; JUNGI, T. W. Toll-like receptors linking innate and adaptive immune response. Veterinary Immunology and Immunopathology, Amsterdam, v. 91, n. 1, p. 91-103, Feb. 2003.
WU, Z.; KAISER, P. Antigen presenting cells in a non-mammalian model system, the chicken. Immunobiology, Stuttgart, v. 216, n. 11, p. 1177-1183, Nov. 2011.
YONEKURA, K.; MAKI-YONEKURA, S.; NAMBA, K. Complete atomic model of the bacterial flagellar filament by electron cryomicroscopy. Nature, London, v. 424, n. 6949, p. 643-650, Aug. 2003.
ZENG, H. et al. Flagellin is the major proinflammatory determinant of
enteropathogenic Salmonella. Journal of Immunology, Baltimore, v. 171, n. 7, p. 3668-3674, Oct. 2003.
SEGUNDA PARTE - ARTIGO
ARTIGO 1 Seleção, caracterização e clonagem dos genes fljB e groEL