Department of Physiology and Pharmacology, Calvin, Joan, and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary Alberta, Canada.
Laboratorio de Inmunología Experimental y Regulación de la Inflamación Hepato-Intestinal, Unidad de Investigación en Biomedicina (UBIMED), Facultad de Estudios Superiores (FES) Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla de Baz, México.
FASEB J. 2019 Apr;33(4):5676-5689. doi: 10.1096/fj.201802160R. Epub 2019 Jan 22.
Macrophages play central roles in immunity as early effectors and modulating adaptive immune reponses; we implicated macrophages in the anticolitic effect of infection with the tapeworm Hymenolepis diminuta. Here, gene arrays revealed that H. diminuta antigen (HdAg) evoked a program in murine macrophages distinct from that elicited by IL-4. Further, HdAg suppressed LPS-evoked release of TNF-α and IL-1β from macrophages via autocrine IL-10 signaling. In assessing the ability of macrophages treated in vitro with an extract of H. diminuta [M] to affect disease, intravenous, but not peritoneal, injection of M protected wild-type but not RAG1 mice from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Administration of splenic CD4 T cells from in vitro cocultures with M, but not those cocultured with M cells, inhibited DNBS-induced colitis; fractionation of the T-cell population indicated that the CD4CD25 T cells from cocultures with M drove the suppression of DNBS-induced colitis. Use of IL-4 or IL-10 CD4 T cells revealed that neither cytokine alone from the donor cells was essential for the anticolitic effect. These data illustrate that HdAg evokes a unique regulatory program in macrophages, identifies HdAg-evoked IL-10 suppression of macrophage activation, and reveals the ability of HdAg-treated macrophages to educate ( i.e., condition) and mobilize CD4CD25 T cells, which could be deployed to treat colonic inflammation.-Reyes, J. L., Lopes, F., Leung, G., Jayme, T. S., Matisz, C. E., Shute, A., Burkhard, R., Carneiro, M., Workentine, M. L., Wang, A., Petri, B., Beck, P. L., Geuking, M. B., McKay, D. M., Macrophages treated with antigen from the tapeworm Hymenolepis diminuta condition CD25 T cells to suppress colitis.
巨噬细胞作为早期效应物和调节适应性免疫反应在免疫中发挥核心作用; 我们发现巨噬细胞参与了带绦虫 Hymenolepis diminuta 感染的抗结肠炎作用。在这里，基因芯片显示 H. diminuta 抗原 (HdAg) 激发了鼠巨噬细胞的一个不同于由 IL-4 激发的程序。此外，HdAg 通过自分泌 IL-10 信号抑制 LPS 诱导的巨噬细胞释放 TNF-α和 IL-1β。在评估用 H. diminuta 提取物体外处理的巨噬细胞 [M] 影响疾病的能力时，静脉内而非腹膜内注射 M 可保护野生型而非 RAG1 小鼠免受二硝基苯磺酸 (DNBS) 诱导的结肠炎。来自与 M 体外共培养的脾 CD4 T 细胞的给药，但不是与 M 细胞共培养的那些细胞的给药，抑制了 DNBS 诱导的结肠炎；T 细胞群体的分离表明，与 M 共培养的 CD4CD25 T 细胞驱动了 DNBS 诱导的结肠炎的抑制。使用 IL-4 或 IL-10 CD4 T 细胞表明，供体细胞中单独的这两种细胞因子都不是抗结肠炎作用所必需的。这些数据表明 HdAg 在巨噬细胞中引发了一个独特的调节程序，确定了 HdAg 诱导的巨噬细胞激活的 IL-10 抑制，并揭示了 HdAg 处理的巨噬细胞教育（即，调节）和动员 CD4CD25 T 细胞的能力，这些细胞可以被部署来治疗结肠炎症。-Reyes, J. L., Lopes, F., Leung, G., Jayme, T. S., Matisz, C. E., Shute, A., Burkhard, R., Carneiro, M., Workentine, M. L., Wang, A., Petri, B., Beck, P. L., Geuking, M. B., McKay, D. M., 用来自带绦虫 Hymenolepis diminuta 的抗原处理的巨噬细胞调节 CD25 T 细胞以抑制结肠炎。
