title: Neonatal CD71+ Erythroid Cells Do Not Modify Murine Sepsis Mortality.
abstract: Sepsis is a major cause of neonatal mortality and morbidity worldwide. A recent report suggested that murine neonatal host defense against infection could be compromised by immunosuppressive CD71(+) erythroid splenocytes. We examined the impact of CD71(+) erythroid splenocytes on murine neonatal mortality to endotoxin challenge or polymicrobial sepsis and characterized circulating CD71(+) erythroid (CD235a(+)) cells in human neonates. Adoptive transfer or an Ab-mediated reduction in neonatal CD71(+) erythroid splenocytes did not alter murine neonatal survival to endotoxin challenge or polymicrobial sepsis challenge. Ex vivo immunosuppression of stimulated adult CD11b(+) cells was not limited to neonatal splenocytes; it also occurred with adult and neonatal bone marrow. Animals treated with anti-CD71 Ab showed reduced splenic bacterial load following bacterial challenge compared with isotype-treated mice. However, adoptive transfer of enriched CD71(+) erythroid splenocytes to CD71(+)-reduced animals did not reduce bacterial clearance. Human CD71(+)CD235a(+) cells were common among cord blood mononuclear cells and were shown to be reticulocytes. In summary, a lack of effect on murine survival to polymicrobial sepsis following adoptive transfer or diminution of CD71(+) erythroid splenocytes under these experimental conditions suggests that the impact of these cells on neonatal infection risk and progression may be limited. An unanticipated immune priming effect of anti-CD71 Ab treatment, rather than a reduction in immunosuppressive CD71(+) erythroid splenocytes, was likely responsible for the reported enhanced bacterial clearance. In humans, the well-described rapid decrease in circulating reticulocytes after birth suggests that they may have a limited role in reducing inflammation secondary to microbial colonization.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232; james.wynn@peds.ufl.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Wynn
authors.affiliation: Department of Dermatology, University of California, Los Angeles, Los Angeles, CA 90095;
authors.forename: Philip O
authors.initials: PO
authors.lastname: Scumpia
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232;
authors.forename: Blair T
authors.initials: BT
authors.lastname: Stocks
authors.affiliation: Division of Neonatology, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232;
authors.forename: Joann
authors.initials: J
authors.lastname: Romano-Keeler
authors.affiliation: Division of Neonatology, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232;
authors.forename: Mhd Wael
authors.initials: MW
authors.lastname: Alrifai
authors.affiliation: Division of Neonatology, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232;
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232;
authors.forename: Annette S
authors.initials: AS
authors.lastname: Kim
authors.affiliation: Department of Pathology, Tennessee Valley Healthcare System, Veterans Affairs, Nashville, TN 37232; and.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Alford
authors.affiliation: Division of Neonatology, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232;
authors.forename: Pranathi
authors.initials: P
authors.lastname: Matta
authors.affiliation: Division of Neonatology, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232;
authors.forename: Jörn-Hendrik
authors.initials: JH
authors.lastname: Weitkamp
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232; Division of Endocrinology, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Moore
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D039481:CD11b Antigen / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D041905:Erythroid Cells / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011990:Receptors, Transferrin / Q000276:immunology*; D012156:Reticulocytes / Q000276:immunology; D018805:Sepsis / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D039481:CD11b Antigen; C068126:CD71 antigen; D004731:Endotoxins; C509295:ITGAM protein, human; D011990:Receptors, Transferrin