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Allele-Specific Induction of IL-1β Expression by C/EBPβ and PU.1 Contributes to Increased Tuberculosis Susceptibility
IL-1β is important for the initial establishment of antimicrobial adaptive immunity, but prolonged IL-1β expression can also cause progressive immunopathology during M. tuberculosis infection. The paradoxical activities of IL-1β in promoting both antimycobacterial immunity and chronic tissue damage have left the ultimate contribution of this cytokine to TB progression in human populations unclear. In this work, we address the role of IL-1β-mediated inflammation using a combination of human genetics and molecular biology, and suggest that exuberant IL-1β responses are causatively associated with TB progression and poor treatment outcome in humans. This work furthers our understanding of the immunological factors that underlie TB disease and provide a strong rationale for the development of specific anti-inflammatory adjunctive therapies that could improve the long-term outcome of TB treatment. In addition, these insights inform the design of future TB control efforts that include the rational design of disease-preventing vaccines and genotype-targeted delivery of TB chemotherapy.
Vyšlo v časopise: Allele-Specific Induction of IL-1β Expression by C/EBPβ and PU.1 Contributes to Increased Tuberculosis Susceptibility. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004426
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004426Souhrn
IL-1β is important for the initial establishment of antimicrobial adaptive immunity, but prolonged IL-1β expression can also cause progressive immunopathology during M. tuberculosis infection. The paradoxical activities of IL-1β in promoting both antimycobacterial immunity and chronic tissue damage have left the ultimate contribution of this cytokine to TB progression in human populations unclear. In this work, we address the role of IL-1β-mediated inflammation using a combination of human genetics and molecular biology, and suggest that exuberant IL-1β responses are causatively associated with TB progression and poor treatment outcome in humans. This work furthers our understanding of the immunological factors that underlie TB disease and provide a strong rationale for the development of specific anti-inflammatory adjunctive therapies that could improve the long-term outcome of TB treatment. In addition, these insights inform the design of future TB control efforts that include the rational design of disease-preventing vaccines and genotype-targeted delivery of TB chemotherapy.
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