Cutting edge: bacterial infection induces hematopoietic stem and progenitor cell expansion in the absence of TLR signaling.
Bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) can be activated by type I IFNs, TLR agonists, viruses, and bacteria to increase hematopoiesis. In this study, we report that endotoxin treatment in vivo induces TLR4, MyD88, and Toll/IL-1 resistance domain-containing adaptor-inducing IFN-beta (TRIF)-dependent expansion of BM HSPCs. Bacterial infection by Staphylococcus aureus or cecal ligation and puncture also induces HSPC expansion, but MyD88, TRIF, type I IFN, cytokine, PG, or oxidative stress pathways are not required for their expansion. S. aureus-induced HSPC expansion in MyD88(-/-)TRIF(-/-) mice is also normal, but is associated with BM remodeling as granulocyte stores are released peripherally. Importantly, reduction in BM cellularity alone can reproduce HSPC expansion. These data show in vivo HSPC responses to bacterial infection are complex and not absolutely dependent upon key inflammatory signaling pathways.
Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610.
Philip O
PO
Scumpia
Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610.
Kindra M
KM
Kelly-Scumpia
Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610.
Matthew J
MJ
Delano
Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610.
Jason S
JS
Weinstein
Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610.
Alex G
AG
Cuenca
Department of Pathology, University of Florida College of Medicine, Gainesville, FL 32610.
Samer
S
Al-Quran
Department of Pathology, University of Florida College of Medicine, Gainesville, FL 32610.
Ian
I
Bovio
Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Shizuo
S
Akira
Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Yutaro
Y
Kumagai
Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610.
Lyle L
LL
Moldawer
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology; D000818:Animals; D001424:Bacterial Infections / Q000209:etiology / Q000276:immunology* / Q000382:microbiology; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002432:Cecum / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008026:Ligation / Q000009:adverse effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
D033942:Adaptor Proteins, Vesicular Transport; D015850:Interleukin-6; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; C470409:TICAM1 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4