title: Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment.
abstract: Toll-like receptors (TLRs) are best known for their ability to recognize microbial or viral components and initiate innate immune responses. We showed here that TLRs and their coreceptors were expressed by multipotential hematopoietic stem cells, whose cell cycle entry was triggered by TLR ligation. TLR expression also extended to some of the early hematopoietic progenitors, although not the progenitor cells dedicated to megakaryocyte and erythroid differentiation. TLR signaling via the Myd88 adaptor protein drove differentiation of myeloid progenitors, bypassing some normal growth and differentiation requirements, and also drove lymphoid progenitors to become dendritic cells. CD14 contributed to the efficiency of lipopolysaccharide (LPS) recognition by stem and progenitor cells, and LPS interacted directly with the TLR4/MD-2 complex on these cells in bone marrow. Thus, the preferential pathogen-mediated stimulation of myeloid differentiation pathways may provide a means for rapid replenishment of the innate immune system during infection.
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104; Division of Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104.
authors.forename: Karla P
authors.initials: KP
authors.lastname: Garrett
authors.affiliation: Division of Immunology, Department of Biomolecular Sciences, Saga Medical School, Saga 849-8501, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Division of Immunology, Department of Biomolecular Sciences, Saga Medical School, Saga 849-8501, Japan.
authors.forename: Uleng
authors.initials: U
authors.lastname: Bahrun
authors.affiliation: Division of Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kouro
authors.affiliation: Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.affiliation: Division of Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104. Electronic address: kincade@omrf.ouhsc.edu.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Kincade
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006098:Granulocytes / Q000166:cytology / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D039902:Multipotent Stem Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88; D023461:Myeloid Progenitor Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000378:metabolism; D051193:Toll-Like Receptors / Q000032:analysis / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors