title: Delayed emergency myelopoiesis following polymicrobial sepsis in neonates.
abstract: Neonates have increased susceptibility to infection, which leads to increased mortality. Whether or not this as a result of implicit deficits in neonatal innate immune function or recapitulation of innate immune effector cell populations following infection is unknown. Here, we examine the process of emergency myelopoiesis whereby the host repopulates peripheral myeloid cells lost following the initial infectious insult. As early inflammatory responses are often dependent upon NF-κB and type I IFN signaling, we also examined whether the absence of MyD88, TRIF or MyD88 and TRIF signaling altered the myelopoietic response in neonates to polymicrobial sepsis. Following neonatal polymicrobial septic challenge, hematopoietic stem cell (HSC) expansion in bone marrow and the spleen were both attenuated and delayed in neonates compared with adults. Similar reductions in other precursors were observed in neonates. Similar to adult studies, the expansion of progenitor stem cell populations was also seen in the absence of MyD88 and/or TRIF signaling. Overall, neonates have impaired emergency myelopoiesis in response to sepsis compared with young adults. Despite reports that this expansion may be related to TLR signaling, our data suggest that other factors may be important, as TRIF(-/-) and MyD88(-/-) neonatal HSCs are still able to expand in response to polymicrobial neonatal sepsis.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Alex G
authors.initials: AG
authors.lastname: Cuenca
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Cuenca
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Lori F
authors.initials: LF
authors.lastname: Gentile
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Saleem
authors.initials: S
authors.lastname: Islam
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Kays
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA shawn.larson@surgery.ufl.edu.
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Larson
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation; D000066673:Cell Self Renewal / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D038042:Myelopoiesis / Q000276:immunology*; D009196:Myeloproliferative Disorders / Q000209:etiology / Q000276:immunology*; D018805:Sepsis / Q000150:complications / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D053594:Myeloid Differentiation Factor 88; C476286:Ticam1 protein, mouse
keywords: LSK; Mice; infection; neutrophil
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