Emani R, Alam C, Pekkala S, Zafar S, Emani M R, Hänninen A
Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
Scand J Immunol. 2015 Feb;81(2):102-9. doi: 10.1111/sji.12253.
Macrophages play a crucial role in innate immune reactions, and peritoneal macrophages (PMs) guard the sterility of this compartment mainly against microbial threat from the gut. Type 1 diabetes (T1D) is an autoimmune disease in which gut microbiota and gut immune system appear to contribute to disease pathogenesis. We have recently reported elevated free radical production and increased permeability of gut epithelium in non-obese diabetic (NOD) mice. Impaired barrier function could lead to bacterial leakage to the peritoneal cavity. To explore the consequences of impaired gut barrier function on extra-intestinal immune regulation, we characterized peritoneal lavage cells from young newly weaned NOD mice. We detected a rapid increase in the number of macrophages 1-2 weeks after weaning in NOD mice compared to C57BL/6 and BALB/c mice. Interestingly, this increase in macrophages was abrogated in NOD mice that were fed an antidiabetogenic diet (ProSobee), which improves gut barrier function. Macrophages in young (5-week-old) NOD mice displayed a poor TNF-α cytokine response to LPS stimulation and high expression of interleukin-1receptor-associated kinase-M (IRAK-M), indicating prior in vivo exposure to TLR-4 ligand(s). Furthermore, injection of LPS intraperitoneally increased T cell CD69 expression in pancreatic lymph node (PaLN), suggestive of T cell activation. Leakage of bacterial components such as endotoxins into the peritoneal cavity may contribute to auto-reactive T cell activation in the PaLN.
巨噬细胞在先天性免疫反应中起关键作用，而腹膜巨噬细胞（PMs）主要保护该腔室的无菌状态，抵御来自肠道的微生物威胁。1型糖尿病（T1D）是一种自身免疫性疾病，其中肠道微生物群和肠道免疫系统似乎参与了疾病的发病机制。我们最近报道，非肥胖糖尿病（NOD）小鼠体内自由基产生增加，肠道上皮通透性增强。屏障功能受损可能导致细菌渗漏至腹腔。为了探究肠道屏障功能受损对肠外免疫调节的影响，我们对刚断奶的年轻NOD小鼠的腹腔灌洗细胞进行了特征分析。与C57BL/6和BALB/c小鼠相比，我们检测到断奶后1-2周NOD小鼠体内巨噬细胞数量迅速增加。有趣的是，在喂食抗糖尿病饮食（ProSobee）的NOD小鼠中，巨噬细胞数量的增加被消除，该饮食可改善肠道屏障功能。年轻（5周龄）NOD小鼠的巨噬细胞对LPS刺激表现出较差的TNF-α细胞因子反应，且白细胞介素-1受体相关激酶-M（IRAK-M）表达较高，表明其体内先前已接触过TLR-4配体。此外，腹腔注射LPS可增加胰腺淋巴结（PaLN）中T细胞CD69的表达，提示T细胞活化。细菌成分如内毒素渗漏至腹腔可能有助于PaLN中自身反应性T细胞的活化。
