Beiting Daniel P, Bliss Susan K, Schlafer Donald H, Roberts Victoria L, Appleton Judith A
James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Infect Immun. 2004 Jun;72(6):3129-37. doi: 10.1128/IAI.72.6.3129-3137.2004.
The aim of this study was to characterize cellular responses to muscle-stage Trichinella spiralis. From its intracellular habitat in muscle, T. spiralis secretes potent glycoprotein antigens that elicit a strong systemic host immune response. Despite the magnitude and prolonged nature of this response, nurse cells are rarely destroyed by infiltrating cells. We tested the hypothesis that the anti-inflammatory cytokine interleukin-10 (IL-10) moderates cellular responses to muscle-stage parasites. Trichinella larvae colonize the diaphragm in large numbers, prompting us to evaluate regional responses in body cavities in addition to local responses in muscle. Mice deficient in IL-10 demonstrated an exaggerated inflammatory response around nurse cells and in the pleural cavity. The effect of IL-10 was most evident 20 days following muscle infection. The increased intensity of the response in IL-10-deficient mice did not affect parasite establishment or survival. Between 20 and 50 days postinfection, the inflammatory response was diminished in both wild-type and IL-10-deficient mice. Muscle infection also elicited an antibody response, characterized initially by mixed isotypes directed at somatic larval antigens and changing to an immunoglobulin G1-dominated response directed at tyvelose-bearing excreted or secreted antigens. We conclude that IL-10 limits local and regional inflammation during the early stages of muscle infection but that chronic inflammation is controlled by an IL-10-independent mechanism that is coincident with a Th2 response.
本研究的目的是描述细胞对旋毛虫肌幼虫期的反应。旋毛虫在肌肉细胞内寄生,可分泌强效糖蛋白抗原,引发强烈的全身性宿主免疫反应。尽管这种反应强烈且持续时间长,但肌幼虫营养细胞很少被浸润细胞破坏。我们检验了如下假说:抗炎细胞因子白细胞介素-10(IL-10)可调节细胞对肌幼虫期寄生虫的反应。旋毛虫幼虫大量寄生于膈肌,这促使我们除了评估肌肉局部反应外,还评估体腔的局部反应。IL-10基因缺失小鼠在肌幼虫营养细胞周围及胸腔表现出过度的炎症反应。IL-10的作用在肌肉感染后20天最为明显。IL-10基因缺失小鼠反应强度增加,但不影响寄生虫的建立或存活。感染后20至50天,野生型和IL-10基因缺失小鼠的炎症反应均减弱。肌肉感染还引发抗体反应,最初表现为针对虫体幼虫抗原的多种抗体亚型混合反应,随后转变为以针对含泰威糖的排泄或分泌抗原的免疫球蛋白G1为主的反应。我们得出结论,IL-10在肌肉感染早期限制局部和区域炎症,但慢性炎症由与Th2反应同时发生的不依赖IL-10的机制控制。