PPE2 protein of Mycobacterium tuberculosis affects myeloid hematopoiesis in mice

Abstract

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.

Keywords: Bone marrow; Hematopoiesis; Infection; Mice; Mycobacterium tuberculosis; PPE2 protein.