M1 macrophage dependent-p53 regulates the intracellular survival of mycobacteria
| Autor: | Sun-Jung Kwon, Ji-Woong Son, Junghwan Lee, Soo-Na Cho, Sang-Hun Son, Chang-Hwa Song, Ji-Ae Choi, Yun-Ji Lim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
p53 Cancer Research Clinical Biochemistry Macrophage polarization Pharmaceutical Science Apoptosis Article Proinflammatory cytokine Microbiology 03 medical and health sciences 0302 clinical medicine Immune system Polarization Macrophage Tuberculosis Pharmacology chemistry.chemical_classification Reactive oxygen species Chemistry Macrophages Biochemistry (medical) Mycobacteria Cell Biology TLR2 030104 developmental biology 030220 oncology & carcinogenesis Intracellular |
| Zdroj: | Apoptosis |
| ISSN: | 1573-675X 1360-8185 |
| Popis: | Tumor suppressor p53 is not only affects immune responses but also contributes to antibacterial activity. However, its bactericidal function during mycobacterial infection remains unclear. In this study, we found that the p53-deficient macrophages failed to control Mycobacterium tuberculosis (Mtb), manifested as a lower apoptotic cell death rate and enhanced intracellular survival. The expression levels of p53 during Mtb infection were stronger in M1 macrophages than in M2 macrophages. The TLR2/JNK signaling pathway plays an essential role in the modulation of M1 macrophage polarization upon Mtb infection. It facilitates p53-mediated apoptosis through the production of reactive oxygen species, nitric oxide and inflammatory cytokines in Mtb-infected M1 macrophages. In addition, nutlin-3 effectively abrogated the intracellular survival of mycobacteria in both TB patients and healthy controls after H37Ra infection for 24 h, indicating that the enhancement of p53 production effectively suppressed the intracellular survival of Mtb in hosts. These results suggest that p53 can be a new therapeutic target for TB therapy. Electronic supplementary material The online version of this article (10.1007/s10495-019-01578-0) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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