title: Natural killer cells regulate murine cytomegalovirus-induced sialadenitis and salivary gland disease.
abstract: The transmission of herpesviruses depends on viral shedding at mucosal surfaces. The salivary gland represents a major site of persistent viral replication for many viruses, including cytomegalovirus. We established a mouse model of salivary gland dysfunction after acute viral infection and investigated the cellular requirements for the loss of secretion. Murine cytomegalovirus (MCMV) infection severely impaired saliva secretion independently of salivary gland virus levels. Lymphocytes or circulating monocytes/macrophages were not required for secretory dysfunction. Dysfunction occurred before glandular inflammation, suggesting that a soluble mediator initiated the disruption of acinar cell function. Despite genetic differences in innate resistance to MCMV, NK cells protected the host against acinar atrophy and the loss of secretions under conditions of an exceedingly low virus inoculum. NK cells also modulated the type of glandular inflammation after infection, as they prevented an influx of Siglec-F(+) polymorphonuclear leukocytes (PMNs). Therefore, beyond their recognized role in controlling MCMV replication, NK cells preserve organ integrity and function and regulate the innate inflammatory response within the gland.
authors.affiliation: Department of Microbiology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Carroll
authors.forename: Alyssa
authors.initials: A
authors.lastname: Lundgren
authors.forename: Hairong
authors.initials: H
authors.lastname: Wei
authors.forename: Susan
authors.initials: S
authors.lastname: Sainz
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Tung
authors.forename: Michael G
authors.initials: MG
authors.lastname: Brown
mesh_terms: D000818:Animals; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000502:physiology*; D012466:Salivary Gland Diseases / Q000276:immunology / Q000378:metabolism / Q000821:virology; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism / Q000821:virology; D012793:Sialadenitis / Q000276:immunology* / Q000378:metabolism / Q000821:virology