RESUMO
Mycobacterium avium has been reported to signal through both Toll-like receptor (TLR2) and TLR9. To investigate the role of TLR6 in innate immune responses to M. avium, TLR6, MyD88, TLR2, and TLR2/6 KO mice were infected with this pathogen. Bacterial burdens were higher in the lungs and livers of infected TLR6, TLR2, TLR2/6, and MyD88 KO mice compared with those in C57BL/6 mice, which indicates that TLR6 is required for the efficient control of M. avium infection. However, TLR6 KO spleen cells presented with normal M. avium induced IFN-γ responses as measured by ELISA and flow cytometry. In contrast, the production of IFN-γ in lung tissue was diminished in all studied KO mice. Furthermore, only MyD88 deficiency reduced granuloma areas in mouse livers. Moreover, we determined that TLR6 plays an important role in controlling bacterial growth within macrophages and in the production of TNF-α, IL-12, and IL-6 by M. avium infected DCs. Finally, the lack of TLR6 reduced activation of MAPKs and NF-κB in DCs. In summary, TLR6 is required for full resistance to M. avium and for the activation of DCs to produce proinflammatory cytokines.
Assuntos
Complexo Mycobacterium avium/imunologia , Infecção por Mycobacterium avium-intracellulare/imunologia , Receptor 6 Toll-Like/imunologia , Animais , Carga Bacteriana/imunologia , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Ativação Enzimática , Granuloma/imunologia , Humanos , Interferon gama/biossíntese , Interferon gama/imunologia , Interleucina-12/biossíntese , Interleucina-6/biossíntese , Fígado/imunologia , Pulmão/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 88 de Diferenciação Mieloide/deficiência , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/imunologia , NF-kappa B/metabolismo , Transdução de Sinais/imunologia , Baço/imunologia , Receptor 2 Toll-Like/deficiência , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/imunologia , Receptor 6 Toll-Like/deficiência , Receptor 6 Toll-Like/genética , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Aim: Characterize the course of acute Aspergillus fumigatus lung infection in immunocompetent mice, investigating the immunological, pathological and tissue functional modifications. Materials & methods: C57BL/6 mice were intranasally infected with A. fumigatus conidia and euthanized to access inflammatory parameters. Results: Mice infected with A. fumigatus showed an inoculum-dependent lethality and body weight loss. An intense proinflammatory cytokine release, neutrophil infiltrate and pulmonary dysfunction was also observed in the early phase of infection. In the late phase of infection, proresolving mediators release, apoptosis and efferocytosis increased and lung tissue architecture is restored. Conclusion: Our study characterized an immunocompetent model of acute pulmonary Aspergillus infection in mice and opened an array of possibilities for investigations on interactions of A. fumigatus with host-immune system.