title: Susceptibility to acute mouse adenovirus type 1 respiratory infection and establishment of protective immunity in neonatal mice.
abstract: There is an incomplete understanding of the differences between neonatal immune responses that contribute to the increased susceptibility of neonates to some viral infections. We tested the hypothesis that neonates are more susceptible than adults to mouse adenovirus type 1 (MAV-1) respiratory infection and are impaired in the ability to generate a protective immune response against a second infection. Following intranasal infection, lung viral loads were greater in neonates than in adults during the acute phase but the virus was cleared from the lungs of neonates as efficiently as it was from adult lungs. Lung gamma interferon (IFN-γ) responses were blunted and delayed in neonates, and lung viral loads were higher in adult IFN-γ(-/-) mice than in IFN-γ(+/+) controls. However, administration of recombinant IFN-γ to neonates had no effect on lung viral loads. Recruitment of inflammatory cells to the airways was impaired in neonates. CD4 and CD8 T cell responses were similar in the lungs of neonates and adults, although a transient increase in regulatory T cells occurred only in the lungs of infected neonates. Infection of neonates led to protection against reinfection later in life that was associated with increased effector memory CD8 T cells in the lungs. We conclude that neonates are more susceptible than adults to acute MAV-1 respiratory infection but are capable of generating protective immune responses.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Megan C
authors.initials: MC
authors.lastname: Procario
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Levine
authors.forename: Mary K
authors.initials: MK
authors.lastname: McCarthy
authors.forename: Eunnie
authors.initials: E
authors.lastname: Kim
authors.forename: Lingqiao
authors.initials: L
authors.lastname: Zhu
authors.forename: Cheong-Hee
authors.initials: CH
authors.lastname: Chang
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
authors.forename: Jason B
authors.initials: JB
authors.lastname: Weinberg
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load
chemical_list: D016207:Cytokines; D007371:Interferon-gamma