NDLI: Beneficial Effects of CpG-Oligodeoxynucleotide Treatment on Trauma and Secondary Lung Infection.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chen, Jianfei Wanke-Jellinek, Lorenz Keegan, Joshua W. Lederer, James A. Dolan, James W. Guo, Fei
Description	Author Affiliation: Wanke-Jellinek L ( Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115); Keegan JW ( Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115); Dolan JW ( Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115); Guo F ( Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115); Chen J ( Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115); Lederer JA ( Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115)
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 TCRÎ³Î´ 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 TCRÎ³Î´ cell-depleted (TCRÎ³Î´(-)) mice to demonstrate that the effects of CpG-ODN on cytokine expression after burn-injury and S. pneumoniae infection rely on functional TCRÎ³Î´ 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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	2
Volume Number	196
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2016-01-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adjuvants, Immunologic Pharmacology Burns Complications Oligodeoxyribonucleotides Pneumonia, Pneumococcal Immunology Animals Disease Models, Animal Immunophenotyping Mass Spectrometry Mice Streptococcus Pneumoniae Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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