Anti-inflammatory Role of Galectin-8 DuringTrypanosoma cruziChronic Infection
Anti-inflammatory Role of Galectin-8 DuringTrypanosoma cruziChronic Infection
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DOI：
10.3389/fcimb.2020.00285
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发表时间：
2020-07-02
影响因子：
5.7
通讯作者：
Leguizamon, Maira S.
中科院分区：
文献类型：
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作者：
Bertelli, Adriano;Sanmarco, Liliana M.;Leguizamon, Maira S.
半乳糖凝集素是对 β-半乳糖苷具有高亲和力的动物凝集素，可通过多种机制驱动免疫反应。特别是半乳糖凝集素 8 (Gal-8) 在炎症中的作用仍存在争议。为了分析其在慢性炎症环境中的作用，我们研究了克氏锥虫感染的小鼠模型。这种寄生虫会引起改变，导致 30% 的感染患者出现慢性心肌病和/或内脏肥大。强烈的心脏炎症和纤维化会导致心肌病，这是恰加斯病最相关的后果。通过分析慢性期（感染后 4-5 个月）受感染的野生型 (iWT) 和 Gal-8 缺陷型 (iGal-8KO) C57BL/6J 小鼠，我们观察到 Gal-8 的缺乏有利于与广泛纤维化相关的心脏、骨骼肌和肝脏炎症普遍增加，与组织寄生虫负荷无关。值得注意的是，通过流式细胞术观察到心脏 iGal-8KO 组织内中性粒细胞和巨噬细胞的频率增加。有人提出，Gal-8 以及其他半乳糖凝集素可诱导活化的中性粒细胞上内分子磷脂酰丝氨酸的表面表达，作为巨噬细胞的“吃我”信号，有利于可行的中性粒细胞去除和组织损伤保护，这一过程称为预瘫痪。我们发现中性粒细胞比率的增加可能与 Gal-8 依赖性预轻瘫的缺失有关，从而导致巨噬细胞中中性粒细胞清除能力减弱。因此，我们的结果支持 Gal-8 在慢性 T 中发挥抗炎作用。克鲁兹感染。
Galectins are animal lectins with high affinity for beta-galactosides that drive the immune response through several mechanisms. In particular, the role of galectin-8 (Gal-8) in inflammation remains controversial. To analyze its role in a chronic inflammatory environment, we studied a murine model ofTrypanosoma cruziinfection. The parasite induces alterations that lead to the development of chronic cardiomyopathy and/or megaviscera in 30% of infected patients. The strong cardiac inflammation along with fibrosis leads to cardiomyopathy, the most relevant consequence of Chagas disease. By analyzing infected wild-type (iWT) and Gal-8-deficient (iGal-8KO) C57BL/6J mice at the chronic phase (4-5 months post-infection), we observed that the lack of Gal-8 favored a generalized increase in heart, skeletal muscle, and liver inflammation associated with extensive fibrosis, unrelated to tissue parasite loads. Remarkably, increased frequencies of neutrophils and macrophages were observed within cardiac iGal-8KO tissue by flow cytometry. It has been proposed that Gal-8, as well as other galectins, induces the surface expression of the inner molecule phosphatidylserine on activated neutrophils, which serves as an "eat-me" signal for macrophages, favoring viable neutrophil removal and tissue injury protection, a process known as preaparesis. We found that the increased neutrophil rates could be associated with the absence of Gal-8-dependent preaparesis, leading to a diminished neutrophil-clearing capability in macrophages. Thus, our results support that Gal-8 exerts an anti-inflammatory role in chronicT. cruziinfection.