2018, Number 4
IFN-γ induces LL-37 but does not control the intracellular growth of M. tuberculosis in alveolar macrophages
Language: Spanish
References: 13
Page: 267-275
PDF size: 255.75 Kb.
ABSTRACT
Interferon-γ (IFN-γ) is one of the most important cytokines in pulmonary tuberculosis immune responses. Its main function is to activate antimicrobial mechanisms in macrophages. Patients with IFN-γ deficiencies are unable to control M. tuberculosis, thus the addition of rhIFN-γ is an alternative treatment. Objective: To evaluate the effects of recombinant human IFN-γ (rhIFN-γ) on human alveolar macrophages infected with M. tuberculosis. Methods: We infected alveolar macrophages from healthy volunteers with M. tuberculosis H37Rv and treated them with rhIFN-γ to evaluate the gene expression of antimicrobial peptide LL-37 and the IRGM protein (related to autophagy) by real time PCR (qPCR), tumoral necrosis factor-α (TNF-α) production by ELISA and intracellular growth control by colony forming units (CFU) of M. tuberculosis. Results: Uninfected macrophages over expressed IRGM after rhIFN-γ treatment, whereas infected macrophages over expressed LL-37. However, the addition of rhIFN-γ did not have a significant effect on production TNF-α production and intracellular growth control of M. tuberculosis. Conclusion: Although LL-37 expression was induced, it was not associated with the killing of M. tuberculosis, suggesting that there are IFN-γ-independent mechanisms involved in the pathogen elimination.REFERENCES
Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment–2017; Ahmad N, Ahuja SD, Akkerman OW, et al. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet 2018;392(10150):821-834. doi: 10.1016/S0140- 6736(18)31644-1.
Zhang X, Falagas ME, Vardakas KZ, et al. Systematic review and meta-analysis of the efficacy and safety of therapy with linezolid containing regimens in the treatment of multidrug-resistant and extensively drugresistant tuberculosis. J Thorac Dis 2015;7(4):603-615. doi: 10.3978/j.issn.2072-1439.2015.03.10.