Klf10 favors Mycobacterium tuberculosis survival by impairing IFN-γ production and preventing macrophages reprograming to macropinocytosis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Edgardo Madrid-Paulino¹  Dulce Mata-Espinosa²  Juan Carlos León-Contreras²  Isela Serrano-Fujarte³  Sol Díaz de León-Guerrero¹  Tomás Villaseñor¹  Lucero Ramon-Luing⁴  José L. Puente³  Leslie Chavez-Galan⁴  Rogelio Hernández-Pando²  Leonor Pérez-Martínez¹  Gustavo Pedraza-Alva¹ 

[1] Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México;Departamento de Patología Experimental, Instituto Nacional de Ciencias Medicas y Nutrición “Salvador Zubirán”;Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México;Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

关键词: Tuberculosis;    Macrophage;    Macropinocytosis;    Interferon gamma;    KLF10;   

DOI  :  10.1002/JLB.4MA0422-288R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY