Prophylactic treatment with Fms-like tyrosine kinase-3 ligand after burn injury enhances global immune responses to infection
Prophylactic treatment with Fms-like tyrosine kinase-3 ligand after burn injury enhances global immune responses to infection
复制标题
DOI：
10.4049/jimmunol.180.5.3038
复制
发表时间：
2008-03-01
影响因子：
4.4
通讯作者：
Toliver-Kinsky, Tracy
中科院分区：
文献类型：
--
作者：
Bohannon, Julia;Cui, Weihua;Toliver-Kinsky, Tracy
严重烧伤患者由于免疫反应改变和频繁的伤口污染而容易受到机会性微生物的感染。免疫调节，以提高全身和局部反应，伤口感染可能是保护烧伤后。我们以前证明，fms样酪氨酸激酶-3（Flt 3）配体（Flt 3L），树突状细胞生长因子，通过树突状细胞依赖性机制增加小鼠对随后的烧伤和伤口感染的抵抗力。本研究旨在检验烧伤后Flt 3L给药通过增强整体免疫细胞活化降低伤口感染易感性的假设。在烧伤后用Flt 3L处理小鼠，并在伤口接种铜绿假单胞菌后检查存活率、伤口和全身细菌清除率以及免疫细胞活化。为了深入了解Flt 3L在烧伤伤口处的局部作用，检查朗格汉斯细胞的定位。用Flt 3L处理的小鼠在感染后而不是感染前具有显著更大数量的表达CD 25的T细胞和表达CD 69的T和B细胞、中性粒细胞和巨噬细胞。Flt 3L处理降低了响应于感染的总体白细胞凋亡。Flt 3L增强了存活以及局部和全身细菌清除。朗格汉斯细胞出现在烧伤创面周围皮肤的真皮中，并在对创面感染的反应中进一步增加。Flt 3L增强了朗格汉斯细胞对损伤和感染的反应。这些数据表明，烧伤后Flt 3L治疗的树突状细胞增强通过促进对感染的局部和全身免疫应答来防止机会性感染。
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.