The commentary of Chirumbolo et al.1 on our recently published article needs to be addressed in s... more The commentary of Chirumbolo et al.1 on our recently published article needs to be addressed in some issues that if not adjusted in this reply may lead to misunderstandings. The concerns give us the opportunity to provide the reader with more details on the clinical data of our patient and with deeper insights into our test performances that might have been too restricted in our original case presentation.In their comment Chirumbolo et al. This article is protected by copyright. All rights reserved.
During experimental tuberculosis (TB), interleukin (IL)-17A appears to be involved in the formati... more During experimental tuberculosis (TB), interleukin (IL)-17A appears to be involved in the formation of lung granulomas, possibly through the attraction of neutrophils to the sites of infection. However, the protective impact of cytokine appears to depend on the degree of its induction. Hence, robust production of IL-17A in mice infected with the hypervirulent isolate Mycobacterium tuberculosis (Mtb) HN878 mediates protection, while the cytokine is dispensable for protective immune responses against low-dose infection with the less virulent strain H37rv. Here, we show that after experimental infection with high doses of Mtb H37rv, IL-17A-deficient (−/−) mice exhibited high susceptibility to the infection, which was mediated by the strong accumulation of neutrophils in the infected lung tissue. Accordingly, we observed nearly unrestricted bacterial replication within the neutrophils, indicating that they may serve as a survival niche for Mtb. By use of IL-17A/IL-17F-double-deficient m...
Protective immunity against Trypanosoma cruzi, the causative agent of Chagas disease, depends on ... more Protective immunity against Trypanosoma cruzi, the causative agent of Chagas disease, depends on the activation of macrophages by IFN-γ and IL-17A. In contrast, IL-10 prevents immunopathology. IL-22 belongs to the IL-10 cytokine family and has pleiotropic effects during host defense and immunopathology, however its role in protection and pathology during T. cruzi infection has not been analyzed yet. Therefore, we examined the role of IL-22 in experimental Chagas disease using the reticulotropic Tulahuen strain of T. cruzi. During infection, IL-22 is secreted by CD4-positive cells in an IL-23-dependent fashion. Infected IL-22−/− mice exhibited an increased production of IFN-γ and TNF and displayed enhanced numbers of activated IFN-γ-producing T cells in their spleens. Additionally, the production of IL-10 was increased in IL-22−/− mice upon infection. Macrophage activation and by association the parasitemia was not affected in the absence of IL-22. Apart from a transient increase in ...
BackgroundVirus infections drive COPD exacerbations and progression. Antiviral immunity centres o... more BackgroundVirus infections drive COPD exacerbations and progression. Antiviral immunity centres on the activation of virus-specific CD8+T-cells by viral epitopes presented on major histocompatibility complex (MHC) class I molecules of infected cells. These epitopes are generated by the immunoproteasome, a specialised intracellular protein degradation machine, which is induced by antiviral cytokines in infected cells.MethodsWe analysed the effects of cigarette smoke on cytokine- and virus-mediated induction of the immunoproteasomein vitro,ex vivoandin vivousing RNA and Western blot analyses. CD8+T-cell activation was determined in co-culture assays with cigarette smoke-exposed influenza A virus (IAV)-infected cells. Mass-spectrometry-based analysis of MHC class I-bound peptides uncovered the effects of cigarette smoke on inflammatory antigen presentation in lung cells. IAV-specific CD8+T-cell numbers were determined in patients’ peripheral blood using tetramer technology.ResultsCigar...
The commentary of Chirumbolo et al.1 on our recently published article needs to be addressed in s... more The commentary of Chirumbolo et al.1 on our recently published article needs to be addressed in some issues that if not adjusted in this reply may lead to misunderstandings. The concerns give us the opportunity to provide the reader with more details on the clinical data of our patient and with deeper insights into our test performances that might have been too restricted in our original case presentation.In their comment Chirumbolo et al. This article is protected by copyright. All rights reserved.
During experimental tuberculosis (TB), interleukin (IL)-17A appears to be involved in the formati... more During experimental tuberculosis (TB), interleukin (IL)-17A appears to be involved in the formation of lung granulomas, possibly through the attraction of neutrophils to the sites of infection. However, the protective impact of cytokine appears to depend on the degree of its induction. Hence, robust production of IL-17A in mice infected with the hypervirulent isolate Mycobacterium tuberculosis (Mtb) HN878 mediates protection, while the cytokine is dispensable for protective immune responses against low-dose infection with the less virulent strain H37rv. Here, we show that after experimental infection with high doses of Mtb H37rv, IL-17A-deficient (−/−) mice exhibited high susceptibility to the infection, which was mediated by the strong accumulation of neutrophils in the infected lung tissue. Accordingly, we observed nearly unrestricted bacterial replication within the neutrophils, indicating that they may serve as a survival niche for Mtb. By use of IL-17A/IL-17F-double-deficient m...
Protective immunity against Trypanosoma cruzi, the causative agent of Chagas disease, depends on ... more Protective immunity against Trypanosoma cruzi, the causative agent of Chagas disease, depends on the activation of macrophages by IFN-γ and IL-17A. In contrast, IL-10 prevents immunopathology. IL-22 belongs to the IL-10 cytokine family and has pleiotropic effects during host defense and immunopathology, however its role in protection and pathology during T. cruzi infection has not been analyzed yet. Therefore, we examined the role of IL-22 in experimental Chagas disease using the reticulotropic Tulahuen strain of T. cruzi. During infection, IL-22 is secreted by CD4-positive cells in an IL-23-dependent fashion. Infected IL-22−/− mice exhibited an increased production of IFN-γ and TNF and displayed enhanced numbers of activated IFN-γ-producing T cells in their spleens. Additionally, the production of IL-10 was increased in IL-22−/− mice upon infection. Macrophage activation and by association the parasitemia was not affected in the absence of IL-22. Apart from a transient increase in ...
BackgroundVirus infections drive COPD exacerbations and progression. Antiviral immunity centres o... more BackgroundVirus infections drive COPD exacerbations and progression. Antiviral immunity centres on the activation of virus-specific CD8+T-cells by viral epitopes presented on major histocompatibility complex (MHC) class I molecules of infected cells. These epitopes are generated by the immunoproteasome, a specialised intracellular protein degradation machine, which is induced by antiviral cytokines in infected cells.MethodsWe analysed the effects of cigarette smoke on cytokine- and virus-mediated induction of the immunoproteasomein vitro,ex vivoandin vivousing RNA and Western blot analyses. CD8+T-cell activation was determined in co-culture assays with cigarette smoke-exposed influenza A virus (IAV)-infected cells. Mass-spectrometry-based analysis of MHC class I-bound peptides uncovered the effects of cigarette smoke on inflammatory antigen presentation in lung cells. IAV-specific CD8+T-cell numbers were determined in patients’ peripheral blood using tetramer technology.ResultsCigar...
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