Fms-like tyrosine kinase-3 ligand alters antigen-specific responses to infections after severe burn injury

Julia Bohannon, Geping Fang, Weihua Cui, Edward Sherwood, Tracy Toliver-Kinsky

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Burn patients are susceptible to opportunistic infections partly because of decreased immune functions, especially TH1-driven antigen-specific responses, which are regulated by dendritic cells. The dendritic cell growth factor, fms-like tyrosine kinase-3 ligand (FL), has been shown to increase resistance to Pseudomonas aeruginosa, in a dendritic cell-dependent manner, in a mouse model of burn wound infection. The specific mechanisms of protection are not known. This study tested the hypothesis that FL can enhance production of P. aeruginosa-specific antibodies after burn wound infection. Mice that had been previously exposed to P. aeruginosa were infected after burn injury by wound inoculation or challenged by intraperitoneal injection of heat-killed P. aeruginosa. In response to wound infection, FL treatments enhanced bacterial clearance and induced a shift from immunoglobulin (Ig) M toward IgG and IgA. However, serum levels of neither P. aeruginosa-specific antibodies nor interferon γ (IFN-γ) were significantly increased by FL, possibly because of decreased systemic exposure to bacteria. After challenge with heat-killed bacteria, which ensured equal exposures, FL-treated mice produced significantly greater levels of P. aeruginosa-specific IgG2a, which correlated with an increase in serum levels of interferon γ and enhanced opsonization capacity. IL-12, IL-10, and transforming growth factor β were significantly increased in FL-treated mice, regardless of the type of challenge. These findings indicate that FL treatments after burn injury enhance cytokine responses to recall antigens and increase bacterial clearance. In addition, through its ability to promote TH1-associated antigen-specific responses, FL may have potential as an immunotherapy to enhance adaptive immunity after severe burn injury.

Original languageEnglish (US)
Pages (from-to)435-441
Number of pages7
JournalShock
Volume32
Issue number4
DOIs
StatePublished - Oct 2009

Fingerprint

Pseudomonas aeruginosa
Antigens
Wounds and Injuries
Wound Infection
Infection
Dendritic Cells
Interferons
Hot Temperature
Bacteria
Bacterial Antigens
Antibodies
Opportunistic Infections
Transforming Growth Factors
Adaptive Immunity
Interleukin-12
Intraperitoneal Injections
Serum
Interleukin-10
Immunotherapy
Immunoglobulin A

Keywords

  • Burn
  • Dendritic cells
  • Humoral
  • Infection

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Fms-like tyrosine kinase-3 ligand alters antigen-specific responses to infections after severe burn injury. / Bohannon, Julia; Fang, Geping; Cui, Weihua; Sherwood, Edward; Toliver-Kinsky, Tracy.

In: Shock, Vol. 32, No. 4, 10.2009, p. 435-441.

Research output: Contribution to journalArticle

Bohannon, Julia ; Fang, Geping ; Cui, Weihua ; Sherwood, Edward ; Toliver-Kinsky, Tracy. / Fms-like tyrosine kinase-3 ligand alters antigen-specific responses to infections after severe burn injury. In: Shock. 2009 ; Vol. 32, No. 4. pp. 435-441.
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