title: Effects of mycobacterial infection on proliferation of hematopoietic precursor cells.
abstract: Bacterial infection can affect hematopoietic precursor cells in bone marrow, because the infected tissues produce various cytokines and chemokines. Little is known about hematopoietic precursor cells, including hematopoietic stem cells and their progenitors, during mycobacterial infection. Here, we showed that mycobacterial infections result in the expansion of not only the lin-c-kit+sca-1+ (LKS+) cell population, but also granulocyte-monocyte progenitor cells in a chronic murine tuberculosis model. Interestingly, stimulation of LKS+ cells with attenuated Mycobacterium tuberculosis H37Ra culture filtrate (RaCF) was significantly stronger than that by virulent H37Rv culture filtrate (RvCF). Lower TNF-α and IL-6 levels were observed in RvCF-stimulated bone marrow cells. Neutralization of TNF-α or IL-6 in RaCF-stimulated bone marrow cells markedly suppressed LKS+ cell clonal expansion. Additionally, numbers of LKS+ cells were lower in TLR2(-/-) and MyD88(-/-) mice after mycobacterial infection. Taken together, LKS+ cell proliferation related to mycobacterial virulence may be related to the secretion of TNF-α and IL-6 associated with TLR signaling. Expansion of hematopoietic progenitor cells may, therefore, play an important role during mycobacterial infection.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jungku, Daejeon 301 747, Republic of Korea.
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Choi
authors.forename: Kwang-Kyu
authors.initials: KK
authors.lastname: Kim
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.forename: Chang-Hwa
authors.initials: CH
authors.lastname: Song
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D017077:Culture Media, Conditioned; D015850:Interleukin-6; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D019009:Proto-Oncogene Proteins c-kit