Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan, USA Graduate Program of Immunology, Medical School, University of Michigan, Ann Arbor, Michigan, USA.
Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan, USA.
J Virol. 2014 Jun;88(12):6934-43. doi: 10.1128/JVI.00204-14. Epub 2014 Apr 2.
Microfold (M) cells are specialized intestinal epithelial cells that internalize particulate antigens and aid in the establishment of immune responses to enteric pathogens. M cells have also been suggested as a portal for pathogen entry into the host. While virus particles have been observed in M cells, it is not known whether viruses use M cells to initiate a productive infection. Noroviruses (NoVs) are single-stranded RNA viruses that infect host organisms via the fecal-oral route. Murine NoV (MNV) infects intestinal macrophages and dendritic cells and provides a tractable experimental system for understanding how an enteric virus overcomes the intestinal epithelial barrier to infect underlying target cells. We found that replication of two divergent MNV strains was reduced in mice depleted of M cells. Reoviruses are double-stranded RNA viruses that infect hosts via respiratory or enteric routes. In contrast to MNV, reovirus infects enterocytes in the intestine. Despite differences in cell tropism, reovirus infection was also reduced in M cell-depleted mice. These data demonstrate that M cells are required for the pathogenesis of two unrelated enteric viruses that replicate in different cell types within the intestine.
To successfully infect their hosts, pathogens that infect via the gastrointestinal tract must overcome the multilayered system of host defenses. Microfold (M) cells are specialized intestinal epithelial cells that internalize particulate antigens and aid in the establishment of immune responses to enteric pathogens. Virus particles have been observed within M cells. However, it is not known whether viruses use M cells to initiate a productive infection. To address this question, we use MNV and reovirus, two enteric viruses that replicate in different cell types in the intestine, intestinal epithelial cells for reovirus and intestinal mononuclear phagocytes for MNV. Interestingly, MNV- and reovirus-infected mice depleted of M cells showed reduced viral loads in the intestine. Thus, our work demonstrates the importance of M cells in the pathogenesis of enteric viruses irrespective of the target cell type in which the virus replicates.
微褶（M）细胞是一种专门的肠上皮细胞，可摄取颗粒状抗原，并有助于对肠道病原体建立免疫反应。M 细胞也被认为是病原体进入宿主的门户。虽然已经观察到病毒颗粒存在于 M 细胞中，但尚不清楚病毒是否利用 M 细胞来引发有效感染。诺如病毒（NoV）是一种单链 RNA 病毒，通过粪-口途径感染宿主。鼠诺如病毒（MNV）感染肠道巨噬细胞和树突状细胞，为理解肠道病毒如何克服肠上皮屏障感染潜在靶细胞提供了一个易于处理的实验系统。我们发现，两种不同的 MNV 株的复制在耗尽 M 细胞的小鼠中减少。呼肠孤病毒是一种双链 RNA 病毒，通过呼吸道或肠道途径感染宿主。与 MNV 不同，呼肠孤病毒感染肠道中的肠细胞。尽管细胞嗜性存在差异，但在耗尽 M 细胞的小鼠中，呼肠孤病毒感染也减少了。这些数据表明，M 细胞是两种在肠道内不同细胞类型中复制的无关肠道病毒发病机制所必需的。
要成功感染其宿主，通过胃肠道感染的病原体必须克服宿主防御的多层次系统。微褶（M）细胞是一种专门的肠上皮细胞，可摄取颗粒状抗原，并有助于对肠道病原体建立免疫反应。已经观察到病毒颗粒存在于 M 细胞内。然而，尚不清楚病毒是否利用 M 细胞来引发有效感染。为了解决这个问题，我们使用 MNV 和呼肠孤病毒，这两种在肠道内不同细胞类型中复制的肠道病毒，肠上皮细胞用于呼肠孤病毒，肠单核吞噬细胞用于 MNV。有趣的是，耗尽 M 细胞的 MNV 和呼肠孤病毒感染小鼠在肠道中的病毒载量减少。因此，我们的工作表明，无论病毒在其中复制的靶细胞类型如何，M 细胞在肠道病毒发病机制中都很重要。
