Role for complement in development of Helicobacter-induced gastritis in interleukin-10-deficient mice
Role for complement in development of Helicobacter-induced gastritis in interleukin-10-deficient mice
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DOI：
10.1128/iai.71.12.7140-7148.2003
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发表时间：
2003-12-01
影响因子：
3.1
通讯作者：
Berg, DJ
中科院分区：
文献类型：
--
作者：
Ismail, HF;Zhang, J;Berg, DJ
免疫应答可根除胃螺杆菌感染的机制尚不清楚。我们假设，螺杆菌诱导的补体系统激活可以促进炎症和根除幽门螺杆菌从胃。体外研究表明，猫螺杆菌能激活正常小鼠血清中的补体，但不能激活Rag 2（-/-）小鼠血清中的补体，表明猫螺杆菌能激活Rag 2（-/-）小鼠的补体。猫通过经典途径激活补体。接下来，我们用H.猫野生型小鼠的螺杆菌感染引起轻度的局灶性胃炎，并没有改变血清补体水平。用H.猫引起严重的胃炎。在初始定殖后，IL-10（-/-）小鼠在第8天完全从胃中清除螺杆菌。与野生型小鼠相比，H.猫感染IL-10（-/-）小鼠血清补体水平显著升高。与野生型对照小鼠相比，野生型小鼠的补体耗竭并不影响胃炎症的强度或螺杆菌定植的程度。相反，Helicobacter-infected IL-10（-/-）小鼠的补体耗竭降低了胃炎的严重程度，减少了Helicobacter-induced中性粒细胞向胃中的浸润，并延迟了细菌的清除。在体外研究中，IL-10（-/-）小鼠的刺激脾细胞和中性粒细胞产生的补体产量是野生型小鼠的两倍。用IL-10预处理抑制这种增加。这些研究确定了补体在IL-10（-/-）小鼠对胃螺杆菌的局部免疫应答中的作用，并表明IL-10在补体产生的调节中的作用。
The mechanisms by which the immune response can eradicate gastric Helicobacter infection are unknown. We hypothesized that Helicobacter-induced activation of the complement system could promote both inflammation and eradication of Helicobacter from the stomach. In vitro studies demonstrated that Helicobacter felis activates complement in normal mouse serum but not in serum from Rag2(-/-) mice, indicating that H. felis activates complement through the classical pathway. Next, we infected complement-depleted wild-type control and interieukin-10-deficient (IL-10(-/-)) mice with H. felis. Helicobacter infection of wild-type mice elicited a mild, focal gastritis and did not alter serum complement levels. Infection of IL-10(-/-) mice with H. felis elicited severe gastritis. After the initial colonization, the IL-10(-/-) mice completely cleared Helicobacter from the stomach by day 8. In contrast to wild-type mice, H. felis-infected IL-10(-/-) mice had a marked increase in serum complement levels. Complement depletion of wild-type mice did not affect the intensity of gastric inflammation or the extent of Helicobacter colonization compared to that for the wild-type control mice. In contrast, complement depletion of Helicobacter-infected IL-10(-/-) mice decreased the severity of gastritis, decreased the Helicobacter-induced infiltration of neutrophils into the stomach, and delayed the clearance of bacteria. In vitro studies of stimulated splenocytes and neutrophils from IL-10(-/-) mice produced a twofold increase in complement production compared to that for wild-type mice. Pretreatment with IL-10 inhibited this increase. These studies identify a role for complement in the local immune response to gastric Helicobacter in IL-10(-/-) mice and suggest a roles for IL-10 in the regulation of complement production.