title: Beneficial Effects of CpG-Oligodeoxynucleotide Treatment on Trauma and Secondary Lung Infection.
abstract: Although Streptococcus pneumoniae is usually found as a commensal in healthy individuals, it can act as a pathogen in trauma patients, causing such complications as early-onset pneumonia and sepsis. We discovered that treating mice with an A-class CpG-oligodeoxynucleotide (ODN) at 2 h after traumatic injury significantly improved mouse survival following early-onset secondary lung infection with S. pneumoniae. This study used mass cytometry (cytometry by time-of-flight) and Luminex technologies to characterize the cellular immune response to secondary S. pneumoniae lung infection at 1 and 3 d postinfection. We found increased expression of CD14, CD64, and PD-L1 on F4-80(+) and F4-80(+)CD11c(+) macrophages, CD11c(+) dendritic cells, and CD14(+)CD172a(+) cells after burn-injury and infection, supporting previous reports of innate immune cell activation in sepsis. CpG-ODN treatment at 2 h after burn-injury reversed these effects; improved pathogen clearance; and led to an increased expression of CD25, CD27, MHCII, and IL-17 on or in TCRγδ cells at 1 d postinfection. At 3 d postinfection, CpG-ODN treatment increased the expression of PD-L1 on innate cell subsets. Furthermore, we analyzed cytokine levels in lung-washout samples of TCRγδ cell-depleted (TCRγδ(-)) mice to demonstrate that the effects of CpG-ODN on cytokine expression after burn-injury and S. pneumoniae infection rely on functional TCRγδ cells. In summary, we demonstrate that cytometry by time-of-flight provides an effective strategy to systematically identify specific cellular phenotypic responses to trauma and bacterial pneumonia and to discover changes in immune system phenotypes associated with beneficial immunotherapy.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Department of Trauma Surgery, Technical University of Munich, 81675 Munich, Germany;
authors.forename: Lorenz
authors.initials: L
authors.lastname: Wanke-Jellinek
authors.affiliation: Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Keegan
authors.affiliation: Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
authors.forename: James W
authors.initials: JW
authors.lastname: Dolan
authors.affiliation: Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Burns Institute, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China; and.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Department of Cardiology, Xinquiao Hospital, The Third Military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Jianfei
authors.identifier: http://orcid.org/0000-0002-6786-9283
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; jlederer@rics.bwh.harvard.edu.
authors.forename: James A
authors.initials: JA
authors.lastname: Lederer
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002056:Burns / Q000150:complications*; D004195:Disease Models, Animal; D016130:Immunophenotyping; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D013296:Streptococcus pneumoniae
chemical_list: D000276:Adjuvants, Immunologic; C513200:CpG-A 2336; D009838:Oligodeoxyribonucleotides