Fms-like tyrosine kinase-3 ligand increases resistance to burn wound infection through effects on plasmacytoid dendritic cells

BMC Immunology

Research Article

Monika Vinish¹  Weihua Cui¹  Tracy Toliver-Kinsky¹  Julia K. Bohannon²  Leon Bae³ 

[1] Department of Anesthesiology, University of Texas Medical Branch and Shriners Hospitals for Children, 301 University Boulevard, 77555-0877, Galveston, TX, USA;Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, USA;Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, USA;

关键词: Thermal injury;    Wound infection;    Dendritic cell;    Neutrophil;    Innate immunity;   

DOI  :  10.1186/s12865-016-0188-2

 received in 2016-08-01, accepted in 2016-12-28,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundPatients experiencing large thermal injuries are susceptible to opportunistic infections that can delay recovery and lead to sepsis. Dendritic cells (DC) are important for the detection of pathogens and activation of the innate and acquired immune responses. DCs are significantly decreased in burn patients early after injury, and the development of sepsis is associated with persistent DC depletion. In a murine model of burn wound infection, the enhancement of DCs after injury by treatment with the DC growth factor Fms-like tyrosine kinase-3 ligand (FL) enhances neutrophil migration to infection, improves bacterial clearance, and increases survival in a DC-dependent manner. FL expands the production of both conventional DCs (cDC) and plasmacytoid DCs (pDC). It has been established that cDCs are required for some of the protective effects of FL after burn injury. This study was designed to determine the contribution of the pDC subset.MethodsMice were subjected to full-thickness scald burns under deep anesthesia and were provided analgesia. pDCs were depleted by injection of anti-plasmacytoid dendritic cell antigen-1 antibodies. Survival, bacterial clearance, and neutrophil responses in vivo and in vitro were measured.ResultsDepletion of preexisting pDCs, but not FL-expanded pDCs, abrogated the beneficial effects of FL on survival, bacterial clearance, and neutrophil migration in response to burn wound infection. This requisite role of pDCs for FL-mediated enhancement of neutrophil migratory capacity is not due to direct effects of pDCs on neutrophils. cDCs, but not pDCs, directly increased neutrophil migratory capacity after co-culture.ConclusionsThe protective effects of FL treatment after burn injury are mediated by both pDCs and cDCs. Pharmacological enhancement of both DC subtypes by FL is a potential therapeutic intervention to enhance immune responses to infection and improve outcome after burn injury.

【 授权许可】

CC BY   
© The Author(s). 2017