RESUMO
We studied cytokine proteins and mRNAs in mice with two forms of Toxoplasma gondii pneumonia resulting from reactivation of infection. In the first form, mice were infected with T. gondii, developed and recovered from systemic disease, and then developed pneumonia 3 weeks later. As pulmonary inflammation developed, levels of cytokine mRNAs for gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-10 increased in bronchoalveolar lavage (BAL) cells or lung tissue, and the level of IFN-gamma protein increased in BAL fluid. The second form of pneumonia occurred as a complication of primary cytomegalovirus (CMV) disease in mice with dormant T. gondii infection. During CMV disease, IL-2 mRNA levels decreased in lung tissue, IL-10 protein levels increased in lung tissue, and IL-10 protein levels increased in BAL fluid. As the mice recovered from CMV disease, T. gondii infection was reactivated in the lungs and was manifested as T. gondii pneumonia. During CMV-induced T. gondii pneumonia, IFN-gamma, IL-2, IL-4, and IL-10 mRNA levels increased in BAL cells or lung tissue, and both IFN-gamma and IL-2 protein levels increased in BAL fluid. We concluded that both forms of T. gondii pneumonia are accompanied by increases in both type 1 T-helper and type 2 T-helper cytokine levels in lungs. The mechanism of CMV-induced reactivation of T. gondii infection in lungs may involve local decreases in IL-2 levels and/or increases in IL-10 levels.
Assuntos
Citocinas/metabolismo , Pneumopatias Parasitárias/imunologia , Toxoplasmose Animal/imunologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/genética , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/complicações , Feminino , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-2/genética , Interleucina-2/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Pneumopatias Parasitárias/etiologia , Pneumopatias Parasitárias/genética , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia Viral/complicações , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Recidiva , Fatores de Tempo , Toxoplasmose Animal/etiologia , Toxoplasmose Animal/genéticaRESUMO
Interferon-gamma has well-documented antiviral and immunomodulatory activity, but its role in the control of cytomegalovirus (CMV) infection is not well studied. In a mouse model of murine CMV (MCMV) disease, interferon-gamma concentrations in serum but not in bronchoalveolar lavage fluid increased in response to viral infection. Serum interferon-gamma levels peaked at day 2 in the relatively resistant C57BL/6 mice, and, in contrast, did not peak until day 6 in susceptible BALB/c mice. Mice genetically lacking interferon-gamma (GKO) were more susceptible to MCMV, although strain differences persisted, with C57BL/6 GKO mice experiencing less severe MCMV disease than BALB/c GKO mice. Treatment of MCMV-infected BALB/c mice with exogenous interferon-gamma starting 2 days after viral infection had a modest protective effect at lower interferon-gamma doses (10(4) units), but interferon-gamma therapy markedly increased morbidity and mortality when higher doses (10(5) units) were used. We conclude that interferon-gamma plays a significant role in host response to MCMV and that the cytokine has dose- and time-dependent beneficial and adverse effects.