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Mycobacterium tuberculosis Mce2E suppresses the macrophage innate immune response and promotes epithelial cell proliferation.

ABSTRACT: The intracellular pathogen Mycobacterium tuberculosis (Mtb) can survive in the host and cause disease by interfering with a variety of cellular functions. The mammalian cell entry 2 (mce2) operon of Mtb has been shown to contribute to tuberculosis pathogenicity. However, little is known about the regulatory roles of Mtb Mce2 family proteins towards host cellular functions. Here we show that the Mce2 family protein Mce2E suppressed the macrophage innate immune response and promoted epithelial cell proliferation. Mce2E inhibited activation of the extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathways in a non-canonical D motif (a MAPK-docking motif)-dependent manner, leading to reduced expression of TNF and IL-6 in macrophages. Furthermore, Mce2E promoted proliferation of human lung epithelium-derived lung adenoma A549 cells by inhibiting K48-linked polyubiquitination of eEF1A1 in a β strand region-dependent manner. In summary, Mce2E is a novel multifunctional Mtb virulence factor that regulates host cellular functions in a niche-dependent manner. Our data suggest a potential novel target for TB therapy.

SUBMITTER: Qiang L

PROVIDER: S-EPMC6461940 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Mycobacterium tuberculosis Mce2E suppresses the macrophage innate immune response and promotes epithelial cell proliferation.

Qiang Lihua L Wang Jing J Zhang Yong Y Ge Pupu P Chai Qiyao Q Li Bingxi B Shi Yi Y Zhang Lingqiang L Gao George Fu GF Liu Cui Hua CH

Cellular & molecular immunology 20180323 4

The intracellular pathogen Mycobacterium tuberculosis (Mtb) can survive in the host and cause disease by interfering with a variety of cellular functions. The mammalian cell entry 2 (mce2) operon of Mtb has been shown to contribute to tuberculosis pathogenicity. However, little is known about the regulatory roles of Mtb Mce2 family proteins towards host cellular functions. Here we show that the Mce2 family protein Mce2E suppressed the macrophage innate immune response and promoted epithelial cel ...[more]

PMID: 29572547

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Project description:BackgroundAs a species, Mycobacterium tuberculosis is more diverse than previously thought. In particular, the Beijing family of M. tuberculosis strains is spreading and evaluating throughout the world and this is giving rise to public health concerns. Genetic diversity within this family has recently been delineated further and a specific genotype, called Bmyc10, has been shown to represent over 60% of all Beijing clinical isolates in several parts of the world. How the host immune system senses and responds to various M. tuberculosis strains may profoundly influence clinical outcome and the relative epidemiological success of the different mycobacterial lineages. We hypothesised that the success of the Bmyc10 group may, at least in part, rely upon its ability to alter innate immune responses and the secretion of cytokines and chemokines by host phagocytes.Methodology/principal findingsWe infected human macrophages and dendritic cells with a collection of genetically well-defined M. tuberculosis clinical isolates belonging to various mycobacterial families, including Beijing. We analyzed cytokine and chemokine secretion on a semi-global level using antibody arrays allowing the detection of sixty-five immunity-related soluble molecules. Our data indicate that Beijing strains induce significantly less interleukin (IL)-6, tumor necrosis factor (TNF), IL-10 and GRO-? than the H37Rv reference strain, a feature that is variously shared by other modern and ancient M. tuberculosis families and which constitutes a signature of the Beijing family as a whole. However, Beijing strains did not differ relative to each other in their ability to modulate cytokine secretion.Conclusions/significanceOur results confirm and expand upon previous reports showing that M. tuberculosis Beijing strains in general are poor in vitro cytokine inducers in human phagocytes. The results suggest that the epidemiological success of the Beijing Bmyc10 is unlikely to rely upon any specific ability of this group of strains to impair anti-mycobacterial innate immunity.

Dataset Information

Mycobacterium tuberculosis Mce2E suppresses the macrophage innate immune response and promotes epithelial cell proliferation.

Publications

Mycobacterium tuberculosis Mce2E suppresses the macrophage innate immune response and promotes epithelial cell proliferation.

Similar Datasets

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