The early secreted antigenic target of 6 kD of Mycobacterium tuberculosis inhibits the proliferation and differentiation of human peripheral blood CD34+ cells. (December 2016)

• Record Type: Journal Article
• Authors: Yi, Na; Jung, Bock-Gie; Wang, Xisheng; Vankayalapati, RamaKrishna; Samten, Buka
• Is Part Of: Tuberculosis. Volume 101(2016)Supplement 1
• Page Start: S28
• Page End: S34
• Publication Date: 2016-12
• Subjects: ESAT-6 -- Mycobacterium tuberculosis -- CD34+ cells -- Differentiation -- Human; 616.995
• DOI: 10.1016/j.tube.2016.09.018
• Languages: English
• ISSNs: 1472-9792

Abstract

Summary: 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.