超过90％的非细菌性胃肠炎疫情由人类诺如病毒（NoVs）引起，这种病毒在大多数人中持续存在，使其在全球范围内传播。这导致了大量地方性病例和发展中国家的7万儿童死亡。诺如病毒主要通过粪-口途径传播。到目前为止，研究主要集中于肠道微生物群对黏膜免疫清除肠道病毒的影响。在本研究中，我们使用了两种持久株小鼠诺如病毒S99（MNoV_S99）和CR6（MNoV_CR6），提供了诺如病毒引起的结肠炎加重依赖于核苷酸结合寡聚化领域2（Nod2）对细菌感应的证据。因此，Nod2缺陷小鼠在两种病毒株的Dextran钠硫酸盐（DSS）诱导结肠炎的严重程度方面显示降低水平。与易受DSS激发的炎症的Atg16l1变态佐剂相比，Nod2缺陷小鼠体内MNoV_CR6血症升高。相应地，来自WT小鼠的巨噬细胞感染可促进信号转导子和转录激活因子1（STAT1）的磷酸化和NOD2的表达水平。这些细胞中测得更高的肿瘤坏死因子α（TNFα）分泌量表明NOD2激活和更好的病毒清除。相反，感染MNoV_S99的Nod2缺陷巨噬细胞显示较低水平的pSTAT1以及TNFα下游分泌的衰减。因此，我们的结果揭示了以前未发现的病毒主机细菌相互作用，可能成为治疗诺如病毒性胃肠炎的新疗法，该疾病可能与常见疾病如克隆病的易感性有关。

Over 90% of epidemic non-bacterial gastroenteritis are caused by human noroviruses (NoVs), which persist in a substantial subset of people allowing their spread worldwide. This has led to a significant number of endemic cases and up to 70,000 children deaths in developing countries. NoVs are primarily transmitted through the fecal-oral route. To date, studies have focused on the influence of the gut microbiota on enteric viral clearance by mucosal immunity. In this study, the use of mouse norovirus S99 (MNoV_S99) and CR6 (MNoV_CR6), two persistent strains, allowed us to provide evidence that the norovirus-induced exacerbation of colitis severity relied on bacterial sensing by nucleotide-binding oligomerization domain 2 (Nod2). Consequently, Nod2-deficient mice showed reduced levels of gravity of Dextran sodium sulfate (DSS)-induced colitis with both viral strains. And MNoV_CR6 viremia was heightened in Nod2-/- mice in comparison with animals hypomorphic for Atg16l1, which are prone to aggravated inflammation under DSS. Accordingly, the infection of macrophages derived from WT mice promoted the phosphorylation of Signal Transducer and Activator of Transcription 1 (STAT1) and NOD2's expression levels. Higher secretion of Tumor Necrosis Factor alpha (TNFα) following NOD2 activation and better viral clearance were measured in these cells. By contrast, reduced levels of pSTAT1 and blunted downstream secretion of TNFα were found in Nod2-deficient macrophages infected by MNoV_S99. Hence, our results uncover a previously unidentified virus-host-bacterial interplay that may represent a novel therapeutic target for treating noroviral origin gastroenteritis that may be linked with susceptibility to several common illnesses such as Crohn's disease.