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Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
The early secreted antigenic target of 6 kD of Mycobacterium tuberculosis inhibits the proliferation and differentiation of human peripheral blood CD34 + cells.
Tuberculosis 2016 December
Abnormalities in hematopoiesis are common in tuberculosis patients and highly prevalent in AIDS patients with tuberculosis coinfection. To explore the potential role of the early secreted antigenic target of 6-kD (ESAT-6) of Mycobacterium tuberculosis (Mtb) in abnormal hematopoiesis in tuberculosis, we studied the effect of ESAT-6 on proliferation and differentiation of in vitro-expanded CD34+ cells isolated from the peripheral blood of the healthy donors. ESAT-6 but not control protein antigen 85A (Ag85A) of Mtb inhibited the proliferation of CD34+ cell derived peripheral blood stem/progenitor cells (PBSPC) in a dose dependent manner when determined by MTT-assay. ESAT-6 but not Ag85A reduced the number of colony forming cells (CFC) of PBSPC by 60-90% as determined by CFC assay by incubation of CD34+ cells in a semi-solid cellulose media in the presence of cytokine cocktail for two weeks. ESAT-6 but not Ag85A increased the percentages of the Annexin-V positive cells and enhanced the cleavage of caspase-3 in PBSPC in a time and dose dependent manner as determined by flow cytometry and Western blot analysis, respectively. ESAT-6 also inhibited murine bone marrow derived non-adherent cell proliferation in response to granulocyte-macrophage colony stimulating factor treatment. We conclude that ESAT-6, an essential virulence factor of Mtb, may contribute to the abnormal hematopoiesis of tuberculosis patients by inhibiting the proliferation and differentiation of hematopoietic cells via apoptosis.
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