Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy



Título del documento: Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy
Revista: Memorias do Instituto Oswaldo Cruz
Base de datos: PERIÓDICA
Número de sistema: 000405458
ISSN: 0074-0276
Autors: 2
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Institucions: 1Instituto Nacional de Ciencia e Tecnologia em Doencas Tropicais, Salvador, Bahia. Brasil
2Universidade Federal da Bahia, Hospital Universitario Professor Edgard Santos, Salvador, Bahia. Brasil
Any:
Període: Abr
Volum: 112
Número: 4
Paginació: 260-268
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés Leprosy or hansen’s disease is a spectral disease whose clinical forms mostly depends on host’s immune and genetic factors. Different Toll-like receptors (TLR) variants have been described associated with leprosy, but with some lack of replication across different populations. OBJECTIVES To evaluate the role of polymorphisms in genes TLR1, TLR2 and TLR4 and susceptibility to leprosy in a genetic case control study; to verify the association between genotypes of these markers and the immunological profile in the serum of patients with leprosy. METHODS Pre-designed TaqMan® assays were used to genotype markers at TLR1 (rs4833095, rs5743551), TLR2 (rs7656411, rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in the serum of a subgroup of patients with and without leprosy reactions. FINDINGS Our results show an association between the T allele of rs3804099 at the TLR2 gene and increased risk for leprosy per se [Odds ratio (OR) = 1.296, p = 0,022]. In addition, evaluating the association between different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine serological levels, IL-17 appears as an immunological marker regulated by the polymorphism of the three TLR genes evaluated, whereas different TLR1 genotypes were associated with differential production of IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and IL-1β was related to TLR4 genotypes. MAIN CONCLUSIONS All together our data points that the tested TLR markers may have a regulatory role in the immunity against Mycobacterium leprae, by driving the host’s production of key cytokines and chemokines involved in the pathogenesis of this disease
Disciplines Medicina
Paraules clau: Dermatología,
Microbiología,
Genética,
Lepra,
Polimorfismo genético,
Susceptibilidad a infecciones,
Perfil inmunológico,
Citocinas,
Quimocinas
Keyword: Medicine,
Dermatology,
Microbiology,
Genetics,
Leprosy,
Genetic polymorphism,
Infections susceptibility,
Immune profile,
Cytokines,
Chemokines
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