title: Allergic airway disease in mice alters T and B cell responses during an acute respiratory poxvirus infection.
abstract: Pulmonary viral infections can exacerbate or trigger the development of allergic airway diseases via multiple mechanisms depending upon the infectious agent. Respiratory vaccinia virus transmission is well established, yet the effects of allergic airway disease on the host response to intra-pulmonary vaccinia virus infection remain poorly defined. As shown here BALB/c mice with preexisting airway disease infected with vaccinia virus developed more severe pulmonary inflammation, higher lung virus titers and greater weight loss compared with mice inoculated with virus alone. This enhanced viremia was observed despite increased pulmonary recruitment of CD8(+) T effectors, greater IFNγ production in the lung, and high serum levels of anti-viral antibodies. Notably, flow cytometric analyses of lung CD8(+) T cells revealed a shift in the hierarchy of immunodominant viral epitopes in virus inoculated mice with allergic airway disease compared to mice treated with virus only. Pulmonary IL-10 production by T cells and antigen presenting cells was detected following virus inoculation of animals and increased dramatically in allergic mice exposed to virus. IL-10 modulation of host responses to this respiratory virus infection was greatly influenced by the localized pulmonary microenvironment. Thus, blocking IL-10 signaling in virus-infected mice with allergic airway disease enhanced pulmonary CD4(+) T cell production of IFNγ and increased serum anti-viral IgG1 levels. In contrast, pulmonary IFNγ and virus-specific IgG1 levels were reduced in vaccinia virus-treated mice with IL-10 receptor blockade. These observations demonstrate that pre-existing allergic lung disease alters the quality and magnitude of immune responses to respiratory poxviruses through an IL-10-dependent mechanism.
authors.affiliation: Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Crystal C
authors.initials: CC
authors.lastname: Walline
authors.forename: Sarita
authors.initials: S
authors.lastname: Sehra
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Fisher
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Guindon
authors.forename: Ian M
authors.initials: IM
authors.lastname: Kratzke
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Montgomery
authors.forename: Kelsey P
authors.initials: KP
authors.lastname: Lipking
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glosson
authors.forename: Heather L
authors.initials: HL
authors.lastname: Benson
authors.forename: George E
authors.initials: GE
authors.lastname: Sandusky
authors.forename: David S
authors.initials: DS
authors.lastname: Wilkes
authors.forename: Randy R
authors.initials: RR
authors.lastname: Brutkiewicz
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.forename: Janice S
authors.initials: JS
authors.lastname: Blum
mesh_terms: D000208:Acute Disease; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001980:Bronchi / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D004848:Epithelium / Q000473:pathology / Q000821:virology; D015726:Giant Cells / Q000473:pathology; D006965:Hyperplasia; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology* / Q000821:virology; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000150:complications / Q000473:pathology / Q000821:virology; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008221:Lymphoid Tissue / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000821:virology; D012141:Respiratory Tract Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D014615:Vaccinia / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D014616:Vaccinia virus / Q000502:physiology*; D019562:Viral Load
chemical_list: D018925:Chemokines; D007074:Immunoglobulin G; D007371:Interferon-gamma