Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Faculdade de Medicina, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Front Immunol. 2022 Jun 29;13:864632. doi: 10.3389/fimmu.2022.864632. eCollection 2022.
IL-17 is a cytokine produced by innate and acquired immunity cells that have an action against fungi and bacteria. However, its action in helminth infections is unclear, including in infection. Toxocariasis is a neglected zoonosis representing a significant public health problem with an estimated seroprevalence of 19% worldwide. In the present study, we describe the immunopathological action of IL-17RA in acute infection. C57BL/6j (WT) and IL-17RA receptor knockout (IL-17RA-/-) mice were infected with 1000 eggs. Mice were evaluated 3 days post-infection for parasite load and white blood cell count. Lung tissue was harvested for histopathology and cytokine expression. In addition, we performed multiparametric flow cytometry in the BAL and peripheral blood, evaluating phenotypic and functional changes in myeloid and lymphoid populations. We showed that IL-17RA is essential to control larvae load in the lung; however, IL-17RA contributed to pulmonary inflammation, inducing inflammatory nodular aggregates formation and presented higher pulmonary IL-6 levels. The absence of IL-17RA was associated with a higher frequency of neutrophils as a source of IL-4 in BAL, while in the presence of IL-17RA, mice display a higher frequency of alveolar macrophages expressing the same cytokine. Taken together, this study indicates that neutrophils may be an important source of IL-4 in the lungs during infection. Furthermore, IL-17/IL-17RA axis is important to control parasite load, however, its presence triggers lung inflammation that can lead to tissue damage.
白细胞介素 17（IL-17）是先天和获得性免疫细胞产生的细胞因子，对真菌和细菌具有作用。然而，其在寄生虫感染中的作用尚不清楚，包括 感染。旋毛虫病是一种被忽视的人畜共患病，在全球范围内估计有 19%的血清流行率，代表着一个重大的公共卫生问题。在本研究中，我们描述了白细胞介素 17 受体（IL-17RA）在急性 感染中的免疫病理作用。C57BL/6j（WT）和 IL-17RA 受体敲除（IL-17RA-/-）小鼠感染 1000 个 虫卵。感染后 3 天评估寄生虫负荷和白细胞计数。采集肺组织进行组织病理学和细胞因子表达分析。此外，我们在 BAL 和外周血中进行了多参数流式细胞术，评估髓样和淋巴样群体的表型和功能变化。我们表明，IL-17RA 对于控制肺部幼虫负荷至关重要；然而，IL-17RA 有助于肺部炎症，诱导炎症性结节聚集形成，并表现出更高的肺组织 IL-6 水平。IL-17RA 的缺失与 BAL 中 IL-4 来源的中性粒细胞频率增加有关，而在存在 IL-17RA 的情况下，小鼠显示表达相同细胞因子的肺泡巨噬细胞频率更高。综上所述，这项研究表明，中性粒细胞可能是 感染期间肺部 IL-4 的重要来源。此外，IL-17/IL-17RA 轴对于控制寄生虫负荷很重要，但它的存在会引发肺部炎症，从而导致组织损伤。
