RESUMO
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a low virulence mycobacterium, and the outcome of disease is dependent on the host genetics for either susceptibility per se or severity. The IFNG gene codes for interferon-γ (IFN-γ), a cytokine that plays a key role in host defense against intracellular pathogens. Indeed, single nucleotide polymorphisms (SNPs) in IFNG have been evaluated in several genetic epidemiological studies, and the SNP +874T>A, the +874T allele, more specifically, has been associated with protection against infectious diseases, especially tuberculosis. Here, we evaluated the association of the IFNG locus with leprosy enrolling 2,125 Brazilian subjects. First, we conducted a case-control study with subjects recruited from the state of São Paulo, using the +874 T>A (rs2430561), +2109 A>G (rs1861494) and rs2069727 SNPs. Then, a second study including 1,370 individuals from Rio de Janeiro was conducted. Results of the case-control studies have shown a protective effect for +874T carriers (OR(adjusted) = 0.75; p = 0.005 for both studies combined), which was corroborated when these studies were compared with literature data. No association was found between the SNP +874T>A and the quantitative Mitsuda response. Nevertheless, the spontaneous IFN-γ release by peripheral blood mononuclear cells was higher among +874T carriers. The results shown here along with a previously reported meta-analysis of tuberculosis studies indicate that the SNP +874T>A plays a role in resistance to mycobacterial diseases.
Assuntos
Interferon gama/genética , Hanseníase/genética , Polimorfismo de Nucleotídeo Único , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Predisposição Genética para Doença , Humanos , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/isolamento & purificação , Razão de Chances , Fatores de RiscoRESUMO
Leprosy is a complex infectious disease influenced by genetic and environmental factors. The genetic contributing factors are considered heterogeneous and several genes have been consistently associated with susceptibility like PARK2, tumor necrosis factor (TNF), lymphotoxin-alpha (LTA) and vitamin-D receptor (VDR). Here, we combined a case-control study (374 patients and 380 controls), with meta-analysis (5 studies; 2702 individuals) and biological study to test the epidemiological and physiological relevance of the interleukin-10 (IL-10) genetic markers in leprosy. We observed that the -819T allele is associated with leprosy susceptibility either in the case-control or in the meta-analysis studies. Haplotypes combining promoter single-nucleotide polymorphisms also implicated a haplotype carrying the -819T allele in leprosy susceptibility (odds ratio (OR)=1.40; P=0.01). Finally, we tested IL-10 production in peripheral blood mononuclear cells stimulated with Mycobacterium leprae antigens and found that -819T carriers produced lower levels of IL-10 when compared with non-carriers. Taken together, these data suggest that low levels of IL-10 during the disease outcome can drive patients to a chronic and unprotective response that culminates with leprosy.
Assuntos
Predisposição Genética para Doença/genética , Interleucina-10/genética , Hanseníase/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Antígenos de Bactérias/imunologia , Estudos de Casos e Controles , Doença Crônica , Feminino , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Marcadores Genéticos/genética , Marcadores Genéticos/imunologia , Predisposição Genética para Doença/epidemiologia , Humanos , Interleucina-10/biossíntese , Interleucina-10/imunologia , Hanseníase/epidemiologia , Hanseníase/imunologia , Hanseníase/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Epidemiologia Molecular/métodos , Mycobacterium leprae/imunologia , Regiões Promotoras Genéticas/imunologiaRESUMO
Piauçus (Leporinus macrocephalus), were raised in 300 m2 ponds (density of 10 fish/m2) presenting asphyxia signals and daily mortality of 27 fishes. Specimens with 8-cm total body length, were collected for necropsy. Mucus of body surface and pieces of organs were collected and examined microscopically, in wet mounts, stained or in histological sections. The smears examination showed the presence of several spores in the secondary lamellae of the gill filaments, identified as Henneguya leporinicola n.sp (Myxozoa: Myxobolidae). Histopathological study showed epithelial hyperplasia and fulfilling of the spaces between the secondary lamellae, congestion and telangiectasia sinusoidal. It was also observed hyperplasia of the goblet cells and several cysts of parasite with 70.3 microns diameter. Such cysts were situated among the secondary lamellae, covered or not by the hyperplasic epithelium. With this diagnostic, three applications of formalin solution 10 ml/m3 were carried out. Fifteen days after that, fish were examined again to ascertain whether the treatment was efficient on disease caused by the protozoa. The tissue alterations present in the gills after the treatment were just a moderate sinusoidal congestion and a slight epithelial hyperplasia on the base of the secondary lamellae.
