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- Title
Klf10 favors Mycobacterium tuberculosis survival by impairing IFN‐γ production and preventing macrophages reprograming to macropinocytosis.
- Authors
Madrid‐Paulino, Edgardo; Mata‐Espinosa, Dulce; León‐Contreras, Juan Carlos; Serrano‐Fujarte, Isela; Díaz de León‐Guerrero, Sol; Villaseñor, Tomás; Ramon‐Luing, Lucero; Puente, José L.; Chavez‐Galan, Leslie; Hernández‐Pando, Rogelio; Pérez‐Martínez, Leonor; Pedraza‐Alva, Gustavo
- Abstract
Mycobacterium tuberculosis has developed diverse mechanisms to survive inside phagocytic cells, such as macrophages. Phagocytosis is a key process in eliminating invading pathogens; thus, M. tuberculosis efficiently disrupts phagosome maturation to ensure infection. However, inflammatory cytokines produced by macrophages in response to early M. tuberculosis infection are key to promoting bacterial clarification. IFN‐γ enhances M. tuberculosis engulfment and destruction by reprogramming macrophages from phagocytosis to macropinocytosis. Here, we show that the transcription factor Krüppel‐like factor 10 (Klf10) plays a positive role in M. tuberculosis survival and infection by negatively modulating IFN‐γ levels. Naïve Klf10‐deficient macrophages produce more IFN‐γ upon stimulation than wild‐type macrophages, thus enhancing bacterial uptake and bactericidal activity achieved by macropinocytosis. Moreover, Klf10⁻/⁻ macrophages showed cytoplasmic distribution of coronin 1 correlated with increased pseudopod count and length. In agreement with these observations, Klf10⁻/⁻ mice showed improved bacterial clearance from the lungs and increased viability. Altogether, our data indicate that Klf10 plays a critical role in M. tuberculosis survival by preventing macrophage reprogramming from phagocytosis to macropinocytosis by negatively regulating IFN‐γ production upon macrophage infection.
- Subjects
MYCOBACTERIUM tuberculosis; PINOCYTOSIS; KRUPPEL-like factors; MACROPHAGES; PHAGOCYTOSIS
- Publication
Journal of Leukocyte Biology, 2022, Vol 112, Issue 3, p475
- ISSN
0741-5400
- Publication type
Article
- DOI
10.1002/JLB.4MA0422-288R