1. Improvement of the resistance against early Mycobacterium tuberculosis-infection in the absence of PI3Kγ enzyme is associated with increase of CD4+IL-17+ cells and neutrophils.
- Author
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Cavalcanti-Neto MP, Prado RQ, Piñeros AR, Sérgio CA, Bertolini TB, Gembre AF, Ramos SG, and Bonato VL
- Subjects
- Animals, Class Ib Phosphatidylinositol 3-Kinase genetics, Disease Models, Animal, Disease Progression, Female, Lung immunology, Lung microbiology, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium tuberculosis immunology, Neutrophil Infiltration, Neutrophils immunology, Neutrophils microbiology, Pneumonia enzymology, Pneumonia immunology, Pneumonia microbiology, Signal Transduction, Th17 Cells immunology, Th17 Cells microbiology, Time Factors, Tuberculosis, Pulmonary microbiology, Tuberculosis, Pulmonary prevention & control, Class Ib Phosphatidylinositol 3-Kinase deficiency, Lung enzymology, Mycobacterium tuberculosis pathogenicity, Neutrophils enzymology, Th17 Cells enzymology, Tuberculosis, Pulmonary enzymology, Tuberculosis, Pulmonary immunology
- Abstract
Given the impossibility to study the lung immune response during Mycobacterium tuberculosis-latent infection, and consequently, the mechanisms that control the bacterial load, it is reasonable to determine the activation of local immunity in the early phase of the infection. The phosphatidylinositol-3-kinase gamma enzyme (PI3Kγ) is involved in the leukocyte recruitment, phagocytosis and cellular differentiation, and therefore, it is considered a promising target for the development of immunotherapies for chronic inflammatory diseases. Mice genetically deficient in PI3Kγ (PI3Kγ
-/- ) or WT (Wild Type) were evaluated 15 days post-infection. The enzyme deficiency improved the resistance against infection, increased the frequency of CD4+ IL-17+ cells, the production of IL-17 as well as the gene and protein expression of molecules associated with Th17 cell differentiation and neutrophil recruitment. Our findings show, for the first time, the participation of the PI3Kγ in vivo in the M. tuberculosis-infection, and suggest an association of Th17 cells with protection in the early phase of tuberculosis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
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