title: Aerosol inoculation with a sub-lethal influenza virus leads to exacerbated morbidity and pulmonary disease pathogenesis.
abstract: A mouse model has been extensively used to investigate disease intervention approaches and correlates of immunity following influenza virus infection. The majority of studies examining cross-reactive and protective immune responses have used intranasal (IN) virus inoculation; however, infectious aerosols are a common means of transmitting influenza in the human population. In this study, IN and aerosol routes of inoculation were compared and end-points of immunity and disease pathogenesis were evaluated in mice using mouse-adapted H3N2 A/Aichi/2/68 (x31). Aerosol inoculation with sub-lethal x31 levels caused more robust infection, which was characterized by enhanced morbidity, mortality, pulmonary cell infiltration, and inflammation, compared to IN-inoculated mice, as well as higher levels of IL-6 expression in the lung. Treatment with IL-6-blocking antibodies reduced pulmonary infiltrates and lung pathology in aerosol-inoculated mice. This study shows that aerosol inoculation results in a distinctive host response and disease outcome compared to IN inoculation, and suggests a possible role for IL-6 in lung pathogenesis.
authors: Department of Infectious Diseases, University of Georgia, Athens, Georgia 30602, USA.
authors: Jennifer Humberd
authors: JH
authors: Smith
authors: Tamas
authors: T
authors: Nagy
authors: Jamie
authors: J
authors: Barber
authors: Paula
authors: P
authors: Brooks
authors: S Mark
authors: SM
authors: Tompkins
authors: Ralph A
authors: RA
authors: Tripp
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D005260:Female; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000472:pathogenicity*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008171:Lung Diseases / Q000276:immunology / Q000473:pathology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology
chemical_list: D000336:Aerosols