Angelova Vanessa V, Kosile Rita T, Darmadi Matthew, Miskovsky Eleanor G, Fink Marc Y, Menegas Samantha, Wexelblatt Haley, Singer Steven M
Department of Biology, Georgetown University, Washington, DC, United States.
Immunohorizons. 2025 May 30;9(7). doi: 10.1093/immhor/vlaf019.
Giardia duodenalis is an intestinal protozoan parasite common in low- and middle-income countries. Infection is often subclinical, even when it is associated with other pathologies like growth stunting in children. Recent longitudinal cohort studies have found Giardia more frequently in patients with milder symptoms and have even suggested that Giardia reduces rotavirus symptom severity. One potential mechanism for limiting disease severity due to other enteropathogens is the promotion of anti-inflammatory responses that limit pathology. Our lab previously showed that Giardia reduces production of interleukin (IL)-12 by dendritic cells stimulated with Toll-like receptor agonists. In this study, we show that Giardia increases the production of the anti-inflammatory cytokine IL-10 by mouse peritoneal macrophages in response to bacterial lipopolysaccharide. This potentiation is specific to IL-10, as no changes were seen in the production of the proinflammatory cytokine tumor necrosis factor ɑ. Moreover, peritoneal macrophages from mice lacking macrophage galactose-binding lectin, a pathogen recognition receptor that has been previously shown to bind N-acetylgalactosamine, failed to increase IL-10 production after stimulation with Giardia and lipopolysaccharide. Giardia's immunoregulation of the IL-10 response may help us understand the parasite's role in reducing diarrheal severity.
十二指肠贾第虫是一种在低收入和中等收入国家常见的肠道原生动物寄生虫。感染通常是亚临床的，即使它与其他病理状况相关，如儿童生长发育迟缓。最近的纵向队列研究发现，症状较轻的患者中贾第虫感染更为频繁，甚至有人提出贾第虫可减轻轮状病毒症状的严重程度。限制其他肠道病原体所致疾病严重程度的一种潜在机制是促进限制病理变化的抗炎反应。我们实验室先前表明，贾第虫可降低经Toll样受体激动剂刺激的树突状细胞产生白细胞介素（IL）-12的水平。在本研究中，我们发现贾第虫可使小鼠腹腔巨噬细胞在对细菌脂多糖作出反应时增加抗炎细胞因子IL-10的产生。这种增强作用对IL-10具有特异性，因为促炎细胞因子肿瘤坏死因子ɑ的产生未见变化。此外，缺乏巨噬细胞半乳糖结合凝集素（一种先前已证明可结合N-乙酰半乳糖胺的病原体识别受体）的小鼠的腹腔巨噬细胞，在用贾第虫和脂多糖刺激后未能增加IL-10的产生。贾第虫对IL-10反应的免疫调节作用可能有助于我们理解该寄生虫在减轻腹泻严重程度中的作用。
