Prophylactic treatment with fms-like tyrosine kinase-3 ligand after burn injury enhances global immune responses to infection

Julia Bohannon, Weihua Cui, Robert Cox, Rene Przkora, Edward Sherwood, Tracy Toliver-Kinsky

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Severely burned patients are susceptible to infections with opportunistic organisms due to altered immune responses and frequent wound contamination. Immunomodulation to enhance systemic and local responses to wound infections may be protective after burn injury. We previously demonstrated that pretreatments with fms-like tyrosine kinase-3 (Flt3) ligand (Flt3L), a dendritic cell growth factor, increase the resistance of mice to a subsequent burn injury and wound infection by a dendritic cell-dependent mechanism. This study was designed to test the hypothesis that Flt3L administration after burn injury decreases susceptibility to wound infections by enhancing global immune cell activation. Mice were treated with Flt3L after burn injury and examined for survival, wound and systemic bacterial clearance, and immune cell activation after wound inoculation with Pseudomonas aeruginosa. To gain insight into the local effects of Flt3L at the burn wound, localization of Langerhans cells was examined. Mice treated with Flt3L had significantly greater numbers of CD25-expressing T cells and CD69-expressing T and B cells, neutrophils, and macrophages after, but not before, infection. Overall leukocyte apoptosis in response to infection was decreased with Flt3L treatment. Survival and local and systemic bacterial clearance were enhanced by Flt3L. Langerhans cells appeared in the dermis of skin bordering the burn wound, and further increased in response to wound infection. Flt3L augmented the appearance of Langerhans cells in response to both injury and infection. These data suggest that dendritic cell enhancement by Flt3L treatments after burn injury protects against opportunistic infections through promotion of local and systemic immune responses to infection.

Original languageEnglish (US)
Pages (from-to)3038-3048
Number of pages11
JournalJournal of Immunology
Volume180
Issue number5
StatePublished - Mar 1 2008

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Wounds and Injuries
Infection
Wound Infection
Langerhans Cells
Therapeutics
Dendritic Cells
Opportunistic Infections
flt3 ligand protein
T-Lymphocytes
Survival
Immunomodulation
Dermis
Pseudomonas aeruginosa
Intercellular Signaling Peptides and Proteins
Neutrophils
Leukocytes
B-Lymphocytes
Macrophages
Apoptosis
Skin

ASJC Scopus subject areas

  • Immunology

Cite this

Prophylactic treatment with fms-like tyrosine kinase-3 ligand after burn injury enhances global immune responses to infection. / Bohannon, Julia; Cui, Weihua; Cox, Robert; Przkora, Rene; Sherwood, Edward; Toliver-Kinsky, Tracy.

In: Journal of Immunology, Vol. 180, No. 5, 01.03.2008, p. 3038-3048.

Research output: Contribution to journalArticle

Bohannon, Julia ; Cui, Weihua ; Cox, Robert ; Przkora, Rene ; Sherwood, Edward ; Toliver-Kinsky, Tracy. / Prophylactic treatment with fms-like tyrosine kinase-3 ligand after burn injury enhances global immune responses to infection. In: Journal of Immunology. 2008 ; Vol. 180, No. 5. pp. 3038-3048.
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