IL-1R type I-dependent hemopoietic stem cell proliferation is necessary for inflammatory granulopoiesis and reactive neutrophilia.
Infections and inflammation trigger neutrophilias that are supported by a hematopoietic program of accelerated granulopoiesis known as emergency granulopoiesis. The intrinsic factors that drive reactive neutrophilias and emergency granulopoiesis have been inferred but not demonstrated. Here, we show that alum cannot elicit reactive neutrophilias in IL-1R type I (IL-1RI)(-/-) mice, whereas other inflammatory responses, including eosinophilia and Ab production, remain intact. Analysis of this specific impairment revealed an unanticipated role for IL-1RI in supporting increased proliferation by granulocyte/macrophage progenitors and, surprisingly, multipotent progenitors and hematopoietic stem cells (HSC). Indeed, HSC and multipotent progenitor proliferative responses were most suppressed in IL-1RI(-/-) mice, suggesting a critical role for their proliferation in inflammatory granulopoiesis. Whereas IL-1 drives increased HSC proliferation directly in vitro, IL-1RI expression by radiation-resistant host cells was both necessary and sufficient for alum-induced HSC, multipotent progenitor, and granulocyte/macrophage progenitor proliferation and reactive neutrophilias in radiation chimeric mice. Thus, IL-1 plays a necessary, but indirect, role in the support of alum-induced neutrophilias by expanding both pluripotent and myeloid progenitor compartments to accelerate granulopoiesis.
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Yoshihiro
Y
Ueda
Derek W
DW
Cain
Masayuki
M
Kuraoka
Motonari
M
Kondo
Garnett
G
Kelsoe
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology* / Q000276:immunology; D006410:Hematopoiesis / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000276:immunology; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; C041524:aluminum sulfate