Assuntos
Adjuvantes Imunológicos/administração & dosagem , Hiperplasia Epitelial Focal/diagnóstico , Hiperplasia Epitelial Focal/tratamento farmacológico , Imiquimode/administração & dosagem , Linfangiectasia Intestinal/diagnóstico , Linfangiectasia Intestinal/tratamento farmacológico , Administração Tópica , Adolescente , Feminino , Hiperplasia Epitelial Focal/complicações , Humanos , Linfangiectasia Intestinal/complicações , Creme para a Pele/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer TIRAP has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers. METHODS: We assessed the TIRAP S180L variant by melting curve and RFLP analysis in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114 individuals participating in case control studies on sepsis and leprosy in Germany, Turkey and Bangladesh. RESULTS: In Ghana, the TIRAP S180L polymorphism was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9% and 12% of German, Bangladesh and Turkish controls, respectively. No significant association of the heterozygous genotype with sepsis or leprosy was observed. Remarkably, homozygous TIRAP 180L tend to increase the risk of sepsis in the German study (P = 0.04). CONCLUSION: A broad protective effect of TIRAP S180L against infectious diseases per se is not discernible.
Assuntos
Predisposição Genética para Doença , Hanseníase/genética , Malária Falciparum/genética , Glicoproteínas de Membrana/genética , Receptores de Interleucina-1/genética , Sepse/genética , Adolescente , Adulto , Idoso , População Negra , Estudos de Casos e Controles , Feminino , Frequência do Gene , Gana , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Gravidez , Adulto JovemAssuntos
Ciclo Celular , Inibidor de Quinase Dependente de Ciclina p27/biossíntese , Regulação da Expressão Gênica , Melanoma/metabolismo , Nevo Pigmentado/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Ciclo Celular/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Feminino , Regulação da Expressão Gênica/fisiologia , Humanos , Masculino , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Neoplasias Cutâneas/diagnósticoRESUMO
TLRs constitute an essential family of pattern recognition molecules that, through direct recognition of conserved microbial components, initiate inflammatory responses following infection. In this role, TLR1 enables host responses to a variety of bacteria, including pathogenic species of mycobacteria. In this study, we report that I602S, a common single nucleotide polymorphism within TLR1, is associated with aberrant trafficking of the receptor to the cell surface and diminished responses of blood monocytes to bacterial agonists. When expressed in heterologous systems, the TLR1 602S variant, but not the TLR1 602I variant, exhibits the expected deficiencies in trafficking and responsiveness. Among white Europeans, the 602S allele represents the most common single nucleotide polymorphism affecting TLR function identified to date. Surprisingly, the 602S allele is associated with a decreased incidence of leprosy, suggesting that Mycobacterium leprae subverts the TLR system as a mechanism of immune evasion.