IL-13 attenuates gastrointestinal candidiasis in normal and immunodeficient RAG-2-/- mice via peroxisome proliferator-activated receptor-γ activation
IL-13 attenuates gastrointestinal candidiasis in normal and immunodeficient RAG-2-/- mice via peroxisome proliferator-activated receptor-γ activation
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DOI：
10.4049/jimmunol.180.7.4939
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Pipy, Bernard
中科院分区：
文献类型：
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作者：
Coste, Agnes;Lagane, Celine;Pipy, Bernard
我们最近证明，在体外过氧化物酶体增殖物激活受体-γ（过氧化物酶体增殖物激活受体γ）激活小鼠腹腔巨噬细胞的IL-13或过氧化物酶体增殖物激活受体γ配体促进摄取和杀死白色念珠菌通过甘露糖受体过表达。在这项研究中，我们证明了用天然和合成的PPAR γ特异性配体或IL-13腹腔内治疗免疫活性和免疫缺陷（RAG-2（-/-））小鼠，可减少口服酵母感染后8天胃肠道（GI）的白色念珠菌定植。我们还发现，念珠菌GI感染触发盲肠粘膜巨噬细胞募集。IL-13和罗格列酮治疗后，这些粘膜巨噬细胞以及腹膜巨噬细胞过度表达甘露糖受体。处理促进巨噬细胞活化以对抗白色念珠菌，如腹膜巨噬细胞吞噬白色念珠菌和在酵母菌攻击后产生活性氧中间体的能力增加所表明的。这些效应对C.白色念珠菌GI感染和巨噬细胞活化通过用GW 9662（一种选择性PPAR γ拮抗剂）处理小鼠而受到抑制，并且在PPAR γ（+/-）小鼠中减少。总之，这些数据表明IL-13或PPAR γ配体减弱C.白色念珠菌感染的胃肠道通过过氧化物酶体增殖物激活受体γ激活，因此表明，过氧化物酶体增殖物激活受体γ配体可能是治疗价值的食管和胃肠道念珠菌病的免疫功能低下的患者。
We recently demonstrated that in vitro peroxisome proliferator-activated receptor-gamma (PPAR gamma) activation of mouse peritoneal macrophages by IL-13 or PPAR gamma ligands promotes uptake and killing of Candida albicans through mannose receptor overexpression. In this study, we demonstrate that i.p. treatment of immunocompetent, and immunodeficient (RAG-2(-/-)) mice with natural and synthetic PPAR gamma-specific ligands or with IL-13 decreases C albicans colonization of the gastrointestinal (GI) tract 8 days following oral infection with the yeast. We also showed that Candida GI infection triggers macrophage recruitment in cecum mucosa. These mucosal macrophages, as well as peritoneal macrophages, overexpress the mannose receptor after IL-13 and rosiglitazone treatments. The treatments promote macrophage activation against C albicans as suggested by the increased ability of peritoneal macrophages to phagocyte C albicans and to produce reactive oxygen intermediates after yeast challenge. These effects on C. albicans GI infection and on macrophage activation are suppressed by treatment of mice with GW9662, a selective PPAR gamma antagonist, and are reduced in PPAR gamma(+/-) mice. Overall, these data demonstrate that IL-13 or PPAR gamma ligands attenuate C. albicans infection of the GI tract through PPAR gamma activation and hence suggest that PPAR gamma ligands may be of therapeutic value in esophageal and GI candidiasis in immunocompromised patients.