Fms-like tyrosine kinase-3 ligand alters antigen-specific responses to infections after severe burn injury.
Fms-like tyrosine kinase-3 ligand alters antigen-specific responses to infections after severe burn injury.
复制标题
DOI：
10.1097/shk.0b013e31819e2937
复制
发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Toliver-Kinsky T
中科院分区：
文献类型：
--
作者：
Bohannon J;Fang G;Cui W;Sherwood E;Toliver-Kinsky T
烧伤患者容易受到机会性感染，部分原因是免疫功能下降，特别是Th 1驱动的抗原特异性反应，这是由树突状细胞调节的。树突状细胞生长因子，fms样酪氨酸激酶-3配体（FL），已被证明可以增加耐药铜绿假单胞菌，在树突状细胞依赖性的方式，在小鼠烧伤创面感染模型。具体的保护机制尚不清楚。本研究验证了FL可以增强烧伤创面感染后铜绿假单胞菌特异性抗体的产生的假设。先前暴露于铜绿假单胞菌的小鼠在烧伤后通过伤口接种感染，或通过腹膜内注射热灭活的铜绿假单胞菌进行攻击。为了应对伤口感染，FL治疗增强了细菌清除，并诱导从IgM向IgG和伊加的转变。然而，FL未显著增加铜绿假单胞菌特异性抗体和IFN-γ的血清水平，可能是由于全身暴露于细菌减少。在用热灭活的细菌进行攻击（这确保了相等的暴露量）后，FL处理的小鼠产生了显著更高水平的铜绿假单胞菌特异性IgG 2a，这与血清IFN-γ水平的增加和增强的调理作用能力相关。IL-12、IL-10和TGF-β在FL处理的小鼠中显著增加，与攻击类型无关。这些发现表明，烧伤后FL治疗增强了细胞因子对回忆抗原的反应，并增加了细菌清除。此外，通过其促进Th 1相关抗原特异性应答的能力，FL可能具有作为免疫疗法的潜力，以增强严重烧伤后的适应性免疫。
Burn patients are susceptible to opportunistic infections due partly to 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 P. 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 following 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 IgM towards IgG and IgA. However, serum levels of neither P. aeruginosa-specific antibodies nor IFN-γ were significantly increased by FL, possibly due to decreased systemic exposure to bacteria. Following 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 IFN-γ and enhanced opsonization capacity. IL-12, IL-10, and TGF-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. Additionally, through its ability to promote Th1-associated antigen-specific responses, FL may have potential as an immunotherapy to enhance adaptive immunity following severe burn injury.