Leukotrienes are reported to be potent proinflammatory mediators that play a role in the development of several inflammatory diseases such as asthma, rheumatoid arthritis and periodontal disease. Leukotrienes have also been associated with protection against infectious diseases. However, the role of leukotrienes in Mycobacterium tuberculosis infection is not understood. To answer this question, we studied the role of leukotrienes in the protective immune response conferred by prime-boost heterologous immunization against tuberculosis. We immunized BALB/c mice (4-11/group) with subcutaneous BCG vaccine (1 x 10(5) M. bovis BCG) (prime) followed by intramuscular DNA-HSP65 vaccine (100 µg) (boost). During the 30 days following the challenge, the animals were treated by gavage daily with MK-886 (5 mg·kg-1·day-1) to inhibit leukotriene synthesis. We showed that MK-886-treated mice were more susceptible to M. tuberculosis infection by counting the number of M. tuberculosis colony-forming units in lungs. The histopathological analysis showed an impaired influx of leukocytes to the lungs of MK-886-treated mice after infection, confirming the involvement of leukotrienes in the protective immune response against experimental tuberculosis. However, prime-boost-immunized mice treated with MK-886 remained protected after challenge with M. tuberculosis, suggesting that leukotrienes are not required for the protective effect elicited by immunization. Protection against M. tuberculosis challenge achieved by prime-boost immunization in the absence of leukotrienes was accompanied by an increase in IL-17 production in the lungs of these animals, as measured by ELISA. Therefore, these data suggest that the production of IL-17 in MK-886-treated, immunized mice could contribute to the generation of a protective immune response after infection with M. tuberculosis.

O fungo dimórfico Paracoccidioides brasiliensis é o agente etiológico da paracoccidioidomicose, uma doença granulomatosa humana. Recentemente, foi relatado o primeiro caso da doença natural em cães. O sistema complemento é um importante componente efetor da imunidade humoral contra agentes infecciosos. Portanto, o objetivo deste trabalho foi avaliar a ativação da via alternativa do complemento canina pelo P. brasiliensis. Inicialmente, foi avaliada a capacidade de eritrócitos de cobaia, coelho, carneiro, galinha e suíno ativarem a via alternativa do complemento canino. Os eritrócitos de cobaia apresentaram maior capacidade de ativar a via alternative do complemento canino. A atividade hemolítica da via alternativa (AH50) foi avaliada em 27 amostras de soro de cães saldáveis e os valores médios observados foram de 87,2 AH50/ml. Não foi observada diferença significativa ao sexo e idade. A ativação da via alternativa pelo P. brasiliensis foi maior nas amostras de soro de cães adultos quando comparada aos cães filhotes e idosos (p < 0.05). Este é o primeiro relato da ativação da via alternative do complemento canino pelo fungo P. brasiliensis e sugere que pode ter um papel protetor na paracoccidioidomicose canina.

The dimorphic fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis, a human granulomatous disease. Recently the first case of natural disease in dogs was reported. The complement system is an important effector component of humoral immunity against infectious agents. Therefore, the aim of this study was to evaluate the activation of the dog alternative complement pathway by P. brasiliensis. Initially, the ability of erythrocytes of guinea pig, rabbit, sheep, chicken and swine to activate the dog alternative pathway was evaluated. The guinea pig erythrocytes showed the greatest capacity to activate dog alternative pathway. The alternative (AH50) hemolytic activity was evaluated in 27 serum samples from healthy dogs and the mean values were 87.2 AH50/ml. No significant differences were observed in relation to sex and age. The alternative pathway activation by P. brasiliensis was higher in serum samples from adult dogs when compared to puppies and aged dogs (p < 0.05). This is the first report of dog alternative complement pathway activation by P. brasiliensis and suggests that it may play a protective role in canine paracoccidioidomycosis.