RESUMO
Cytokines are considered vital mediators of the immune system. Down- or upregulation of these mediators is linked to several inflammatory and pathologic situations. IL-26 is referred to as an identified member of the IL-10 family and IL-20 subfamily. Due to having a unique cationic structure, IL-26 exerts diverse functions in several diseases. Since IL-26 is mainly secreted from Th17, it is primarily considered a pro-inflammatory cytokine. Upon binding to its receptor complex (IL-10R1/IL-20R2), IL-26 activates multiple signalling mediators, especially STAT1/STAT3. In cancer, IL-26 induces IL-22-producing cells, which consequently decrease cytotoxic T-cell functions and promote tumour growth through activating anti-apoptotic proteins. In hypersensitivity conditions such as rheumatoid arthritis, multiple sclerosis, psoriasis and allergic disease, this cytokine functions primarily as the disease-promoting mediator and might be considered a biomarker for disease prognosis. Although IL-26 exerts antimicrobial function in infections such as hepatitis, tuberculosis and leprosy, it has also been shown that IL-26 might be involved in the pathogenesis and exacerbation of sepsis. Besides, the involvement of IL-26 has been confirmed in other conditions, including graft-versus-host disease and chronic obstructive pulmonary disease. Therefore, due to the multifarious function of this cytokine, it is proposed that the underlying mechanism regarding IL-26 function should be elucidated. Collectively, it is hoped that the examination of IL-26 in several contexts might be promising in predicting disease prognosis and might introduce novel approaches in the treatment of various diseases.
Assuntos
Suscetibilidade a Doenças , Interleucinas/genética , Interleucinas/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica , Humanos , Infecções/etiologia , Infecções/metabolismo , Infecções/patologia , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Interleucinas/química , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Especificidade de Órgãos/genética , Especificidade de Órgãos/imunologia , Transporte Proteico , Transdução de Sinais , Relação Estrutura-AtividadeRESUMO
Variants in the leucine-rich repeat kinase-2 (LRRK2) gene are associated with Parkinson's disease, leprosy, and Crohn's disease, three disorders with inflammation as an important component. Because of its high expression in granulocytes and CD68-positive cells, LRRK2 may have a function in innate immunity. We tested this hypothesis in two ways. First, adult mice were intravenously inoculated with Salmonella typhimurium, resulting in sepsis. Second, newborn mouse pups were intranasally infected with reovirus (serotype 3 Dearing), which induced encephalitis. In both mouse models, wild-type Lrrk2 expression was protective and showed a sex effect, with female Lrrk2-deficient animals not controlling infection as well as males. Mice expressing Lrrk2 carrying the Parkinson's disease-linked p.G2019S mutation controlled infection better, with reduced bacterial growth and longer animal survival during sepsis. This gain-of-function effect conferred by the p.G2019S mutation was mediated by myeloid cells and was abolished in animals expressing a kinase-dead Lrrk2 variant, p.D1994S. Mouse pups with reovirus-induced encephalitis that expressed the p.G2019S Lrrk2 mutation showed increased mortality despite lower viral titers. The p.G2019S mutant Lrrk2 augmented immune cell chemotaxis and generated more reactive oxygen species during virulent infection. Reovirus-infected brains from mice expressing the p.G2019S mutant Lrrk2 contained higher concentrations of α-synuclein. Animals expressing one or two p.D1994S Lrrk2 alleles showed lower mortality from reovirus-induced encephalitis. Thus, Lrrk2 alleles may alter the course of microbial infections by modulating inflammation, and this may be dependent on the sex and genotype of the host as well as the type of pathogen.
Assuntos
Alelos , Infecções/enzimologia , Infecções/genética , Inflamação/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Caracteres Sexuais , Animais , Encéfalo/patologia , Encéfalo/virologia , Quimiotaxia , Encefalite/virologia , Feminino , Humanos , Infecções/imunologia , Infecções/patologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/deficiência , Leucócitos/enzimologia , Masculino , Camundongos Endogâmicos C57BL , Mutação/genética , Espécies Reativas de Oxigênio/metabolismo , Reoviridae/fisiologia , Salmonella typhimurium/crescimento & desenvolvimento , Sepse/microbiologia , Análise de Sobrevida , alfa-Sinucleína/metabolismoAssuntos
Mãos/patologia , Infecções/patologia , Reação no Local da Injeção/patologia , Dor/patologia , Prototheca/isolamento & purificação , Esteroides/efeitos adversos , Feminino , Mãos/microbiologia , Humanos , Infecções/terapia , Reação no Local da Injeção/microbiologia , Reação no Local da Injeção/terapia , Injeções Intramusculares/efeitos adversos , Pessoa de Meia-Idade , Dor/microbiologia , Esteroides/administração & dosagemRESUMO
Interleukin-18 (IL-18) is a novel cytokine mainly produced by activated macrophages. IL-18 was originally called interferon-gamma inducing factor, due to its action in inducing IFN-gamma secretion from Th1 cells, NK cells and NKT cells. It has been reported that IL-18 may play important roles in various diseases including cancer and infectious diseases. This review deals with the roles of IL-18 in infectious diseases, with special emphasis on IL-18 in infectious diseases caused by intracellular pathogens including Mycobacterium tuberculosis, Mycobacterium leprae, Listeria monocytogenes and Salmonella typhimurium.