title: Polymicrobial sepsis induces divergent effects on splenic and peritoneal dendritic cell function in mice.
abstract: Dendritic cells (DCs) are professional antigen-presenting cells that act as sentinels in the cell-mediated response against invading pathogens associated with septic challenge. The purpose of the present study was to determine whether there is a loss of dendritic cells and/or changes in function of these cells in septic mice. Here we report that the number of DCs, in both spleen and peritoneum, decreased over 24 h postsepsis [cecal ligation and puncture (CLP)] when compared with sham. The most dramatic change was seen in the peritoneal cavity. This decrease appeared to be caused mainly by the depletion of immature DCs rather than mature DCs. This change was LPS independent and minimally affected by FasL; however, overexpression of human Bcl-2 gene provides protection of the septic peritoneal DCs. Moreover, although the level of IL-12 release decreased significantly in splenic DCs obtained from CLP mice, IL-12 secretion was markedly elevated by peritoneal DCs as well as in both plasma and peritoneal fluid at 24 h post-CLP. In peritoneal cells, the expression of CD40, CD80, and CD86 was unchanged, but their respective ligands CD40L, CD28, and CD152 all increased in mice 24 h after CLP, although no such change was observed in splenocytes. Regardless of the presence or absence of antigen, peritoneal DCs from CLP mice showed higher capacity to stimulate T-cell proliferation than those cells from the sham control. However, splenic DCs from CLP mice only showed augmented capacity to induce antigen-dependent stimulation of T-cell proliferation. Together, these data indicate that sepsis produces divergent functional changes in splenic and peritoneal DC populations.
authors.affiliation: Division of Surgical Research, Department of Surgery, Rhode Island Hospital, Brown University School of Medicine, Providence, Rhode Island 02903, USA.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Ding
authors.forename: Chun-Shiang
authors.initials: CS
authors.lastname: Chung
authors.forename: Sarah
authors.initials: S
authors.lastname: Newton
authors.forename: Yaping
authors.initials: Y
authors.lastname: Chen
authors.forename: Stacey
authors.initials: S
authors.lastname: Carlton
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Albina
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D039521:CD11c Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D060908:CTLA-4 Antigen; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010533:Peritoneal Lavage; D010537:Peritoneum / Q000378:metabolism; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018805:Sepsis / Q000382:microbiology*; D013154:Spleen / Q000166:cytology* / Q000382:microbiology; D013997:Time Factors; D051197:Toll-Like Receptor 4
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D039521:CD11c Antigen; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D017077:Culture Media, Conditioned; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D018664:Interleukin-12