Efficient norovirus and reovirus replication in the mouse intestine requires microfold (M) cells.
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.


OBJECTIVE
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.
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.
Mariam B
MB
Gonzalez-Hernandez
Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan, USA.
Thomas
T
Liu
Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan, USA.
Hilary C
HC
Payne
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Jennifer E
JE
Stencel-Baerenwald
Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Mine
M
Ikizler
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Hideo
H
Yagita
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Terence S
TS
Dermody
Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA.
Ifor R
IR
Williams
Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan, USA cwobus@umich.edu.
Christiane E
CE
Wobus
D000818:Animals; D017250:Caliciviridae Infections / Q000821:virology*; D002460:Cell Line; D004847:Epithelial Cells / Q000821:virology*; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D029322:Norovirus / Q000502:physiology*; D012087:Reoviridae / Q000502:physiology*; D012088:Reoviridae Infections / Q000821:virology*; D014779:Virus Replication