title: Infection susceptibility and immune senescence with advancing age replicated in accelerated aging Lmna(Dhe) mice.
abstract: Aging confers increased susceptibility to common pathogens including influenza A virus. Despite shared vulnerability to infection with advancing age in humans and rodents, the relatively long time required for immune senescence to take hold practically restricts the use of naturally aged mice to investigate aging-induced immunological shifts. Here, we show accelerated aging Lmna(Dhe) mice with spontaneous mutation in the nuclear scaffolding protein, lamin A, replicate infection susceptibility, and substantial immune cell shifts that occur with advancing age. Naturally aged (≥ 20 month) and 2- to 3-month-old Lmna(Dhe) mice share near identically increased influenza A susceptibility compared with age-matched Lmna(WT) control mice. Increased mortality and higher viral burden after influenza infection in Lmna(Dhe) mice parallel reduced accumulation of lung alveolar macrophage cells, systemic expansion of immune suppressive Foxp3⁺ regulatory T cells, and skewed immune dominance among viral-specific CD8⁺T cells similar to the immunological phenotype of naturally aged mice. Thus, aging-induced infection susceptibility and immune senescence are replicated in accelerated aging Lmna(Dhe) mice.
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital, Cincinnati, OH, 45229, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xin
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital, Cincinnati, OH, 45229, USA.
authors.forename: Tony T
authors.initials: TT
authors.lastname: Jiang
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital, Cincinnati, OH, 45229, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Kinder
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital, Cincinnati, OH, 45229, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Ertelt
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital, Cincinnati, OH, 45229, USA.
authors.forename: Sing Sing
authors.initials: SS
authors.lastname: Way
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D034904:Lamin Type A / Q000235:genetics; D008168:Lung / Q000276:immunology* / Q000821:virology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011371:Progeria / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D034904:Lamin Type A
keywords: accelerated aging; infection susceptibility; models of immune senescence; progeria syndrome