Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Inner Ring Road, Uppal, Hyderabad - 500039, Telangana, India; Manipal Academy of Higher Education, Manipal - 576104, Karnataka, India.
Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Inner Ring Road, Uppal, Hyderabad - 500039, Telangana, India.
Immunobiology. 2021 Jan;226(1):152051. doi: 10.1016/j.imbio.2020.152051. Epub 2020 Dec 3.
Irregularity in hematopoiesis is noted in humans during tuberculosis. However, influence of mycobacterial protein(s) on bone marrow hematopoiesis is not fully understood. In this study, we have demonstrated the role of a mycobacterial protein, PPE2 (Rv0256c) in suppressing hematopoiesis during infection. PPE2 belongs to PPE (proline-proline-glutamine) family of mycobacterial proteins which are well known for hijacking host machineries for better survival inside host. In the present study, we have shown that mice infected with Mycobacterium smegmatis expressing PPE2 (M. smeg-PPE2) had a marked reduction in cells of myeloid lineage in bone marrow and peripheral blood along with altered bone marrow phenotype. Bone marrow of M. smeg-PPE2-infected mice showed an overall hypo-cellularity with an increase in population of immature cells, along with reduction in mature cell population. Higher number of M. smeg-PPE2 bacilli was observed in bone-marrow, lung, liver and spleen of mice as compared to the control mycobacteria (M. smeg-pVV16). M. smeg-PPE2-infected mice also showed higher expression of IFN-γ than those infected with M. smeg-pVV16. We conclude that PPE2 affects bone-marrow hematopoiesis of myeloid cells, probably by increasing IFN-γ levels, both locally and systemically, thus favoring the bacilli to establish a positive infection.
在人类结核病期间，造血功能会出现异常。然而，分枝杆菌蛋白对骨髓造血的影响尚未完全了解。在这项研究中，我们已经证明了分枝杆菌蛋白 PPE2（Rv0256c）在感染期间抑制造血的作用。PPE2 属于分枝杆菌 PPE（脯氨酸-脯氨酸-谷氨酰胺）家族的蛋白，这些蛋白以劫持宿主机制在宿主内更好地生存而闻名。在本研究中，我们表明表达 PPE2 的耻垢分枝杆菌（M. smeg-PPE2）感染的小鼠骨髓和外周血中的髓系细胞明显减少，同时骨髓表型发生改变。M. smeg-PPE2 感染小鼠的骨髓总体呈低细胞性，幼稚细胞群体增加，同时成熟细胞群体减少。与对照分枝杆菌（M. smeg-pVV16）相比，M. smeg-PPE2 感染的小鼠骨髓、肺、肝和脾中的 M. smeg-PPE2 杆菌数量更多。与感染 M. smeg-pVV16 的小鼠相比，M. smeg-PPE2 感染的小鼠也表现出更高水平的 IFN-γ 表达。我们的结论是，PPE2 通过局部和全身增加 IFN-γ 水平来影响骨髓中髓系细胞的造血，从而有利于细菌建立阳性感染。
