Key Points IL-10 is not detrimental to early M. tuberculosis infection outcome. Lack of IL-10 influences immune responses and fibrosis in granulomas. Modeling predicts that prolonged lack of IL-10 leads to improved infection outcomes. Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a major global health problem. Lung granulomas are organized structures of host immune cells that function to contain the bacteria. Cytokine expression is a critical component of the protective immune response, but inappropriate cytokine expression can exacerbate TB. Although the importance of proinflammatory cytokines in controlling M. tuberculosis infection has been established, the effects of anti-inflammatory cytokines, such as IL-10, in TB are less well understood. To investigate the role of IL-10, we used an Ab to neutralize IL-10 in cynomolgus macaques during M. tuberculosis infection. Anti–IL-10–treated nonhuman primates had similar overall disease outcomes compared with untreated control nonhuman primates, but there were immunological changes in granulomas and lymph nodes from anti–IL-10–treated animals. There was less thoracic inflammation and increased cytokine production in lung granulomas and lymph nodes from IL-10–neutralized animals at 3–4 wk postinfection compared with control animals. At 8 wk postinfection, lung granulomas from IL-10–neutralized animals had reduced cytokine production but increased fibrosis relative to control animals. Although these immunological changes did not affect the overall disease burden during the first 8 wk of infection, we paired computational modeling to explore late infection dynamics. Our findings support that early changes occurring in the absence of IL-10 may lead to better bacterial control later during infection. These unique datasets provide insight into the contribution of IL-10 to the immunological balance necessary for granulomas to control bacterial burden and disease pathology in M. tuberculosis infection.

中文翻译：

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IL-10 损害早期结核分枝杆菌感染期间肺肉芽肿和淋巴结的局部免疫反应


要点 IL-10 对早期结核分枝杆菌感染结果无害。 IL-10 的缺乏会影响肉芽肿的免疫反应和纤维化。模型预测长期缺乏 IL-10 会改善感染结果。结核病（TB）由结核分枝杆菌引起，仍然是一个主要的全球健康问题。肺肉芽肿是宿主免疫细胞的组织结构，其功能是遏制细菌。细胞因子表达是保护性免疫反应的关键组成部分，但不适当的细胞因子表达会加剧结核病。尽管促炎细胞因子在控制结核分枝杆菌感染中的重要性已被确​​定，但抗炎细胞因子（例如 IL-10）在结核病中的作用尚不清楚。为了研究 IL-10 的作用，我们使用抗体来中和食蟹猴结核分枝杆菌感染期间的 IL-10。与未经治疗的对照非人灵长类动物相比，抗IL-10治疗的非人灵长类动物具有相似的总体疾病结果，但抗IL-10治疗的动物的肉芽肿和淋巴结存在免疫学变化。与对照动物相比，感染后 3-4 周，IL-10 中和动物的胸部炎症较少，肺肉芽肿和淋巴结中细胞因子的产生增加。感染后 8 周，与对照动物相比，IL-10 中和动物的肺肉芽肿细胞因子产生减少，但纤维化增加。尽管这些免疫学变化并未影响感染前 8 周的总体疾病负担，但我们配对计算模型来探索晚期感染动态。我们的研究结果支持，在没有 IL-10 的情况下发生的早期变化可能会导致感染后期更好的细菌控制。 这些独特的数据集让我们深入了解 IL-10 对肉芽肿控制结核分枝杆菌感染的细菌负荷和疾病病理学所需的免疫平衡的贡献。