title: MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis.
abstract: Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1(+)CD11b(+) population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1(+) cells effectively suppress antigen-specific CD8(+) T cell interferon (IFN) gamma production but only modestly suppress antigen-specific and nonspecific CD4(+) T cell proliferation. GR-1(+) cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell-dependent and depression of Th1 cell-dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain-containing adaptor-inducing IFN-beta, or the IFN-alpha/beta receptor, is required for complete GR-1(+)CD11b(+) expansion. GR-1(+)CD11b(+) cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Delano
authors.forename: Philip O
authors.initials: PO
authors.lastname: Scumpia
authors.forename: Jason S
authors.initials: JS
authors.lastname: Weinstein
authors.forename: Dominique
authors.initials: D
authors.lastname: Coco
authors.forename: Srinivas
authors.initials: S
authors.lastname: Nagaraj
authors.forename: Kindra M
authors.initials: KM
authors.lastname: Kelly-Scumpia
authors.forename: Kerri A
authors.initials: KA
authors.lastname: O'Malley
authors.forename: James L
authors.initials: JL
authors.lastname: Wynn
authors.forename: Svetlana
authors.initials: S
authors.lastname: Antonenko
authors.forename: Samer Z
authors.initials: SZ
authors.lastname: Al-Quran
authors.forename: Ryan
authors.initials: R
authors.lastname: Swan
authors.forename: Chun-Shiang
authors.initials: CS
authors.lastname: Chung
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
authors.forename: Reuben
authors.initials: R
authors.lastname: Ramphal
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Gabrilovich
authors.forename: Wesley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
authors.forename: Joseph
authors.initials: J
authors.lastname: Phillips
authors.forename: Drake
authors.initials: D
authors.lastname: Laface
authors.forename: Paul G
authors.initials: PG
authors.lastname: Heyworth
authors.forename: Michael
authors.initials: M
authors.lastname: Clare-Salzler
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D023461:Myeloid Progenitor Cells / Q000276:immunology* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; C503133:Gr-1 protein, mouse; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D019707:Receptors, Chemokine