Impaired immune response to Candida albicans in aged mice.
The prevalence of opportunistic fungal infections has increased dramatically among the aged population in recent years. This work investigated the effect of ageing on murine defences against Candida albicans. Aged C57BL/6 mice that were experimentally infected intravenously had a significantly impaired survival and a higher tissue fungal burden compared with young mice. In vitro production of tumour necrosis factor (TNF)-alpha by macrophages from aged mice in response to yeast cells and hyphae of C. albicans was significantly lower than production by macrophages from young mice. In vitro production of cytokines, such as TNF-alpha and gamma interferon (IFN-gamma), by antigen-stimulated splenocytes from mice intravenously infected with C. albicans cells was also diminished in old mice. This decrease in production of T helper 1 cytokines in old mice correlated with a diminished frequency of IFN-gamma-producing CD4+ T lymphocytes, although the ability to develop an acquired resistance upon vaccination (primary sublethal infection) of mice with the low-virulence PCA2 strain was not affected in aged mice. The diversity of antigens recognized by C. albicans-specific antibodies in sera from infected aged mice was clearly diminished when compared with that from infected young mice. Taken together, these data show that aged mice develop an altered innate and adaptive immune response to C. albicans and are more susceptible to systemic primary candidiasis.
Murciano
Celia
C
Departamento de Microbiología y Ecología, Universitat de València, Facultad de Ciencias Biológicas, Edificio de Investigación, C/Dr. Moliner 50, 46100 Burjasot, Valencia, Spain.
Villamón
Eva
E
Departamento de Microbiología y Ecología, Universitat de València, Facultad de Ciencias Biológicas, Edificio de Investigación, C/Dr. Moliner 50, 46100 Burjasot, Valencia, Spain.
Yáñez
Alberto
A
Departamento de Microbiología y Ecología, Universitat de València, Facultad de Ciencias Biológicas, Edificio de Investigación, C/Dr. Moliner 50, 46100 Burjasot, Valencia, Spain.
O'Connor
José-Enrique
JE
Laboratorio de Citómica, Unidad Mixta CIPF-UVEG, Centro de Investigación 'Principe Felipe', Valencia, Spain.
Gozalbo
Daniel
D
Departamento de Microbiología y Ecología, Universitat de València, Facultad de Ciencias Biológicas, Edificio de Investigación, C/Dr. Moliner 50, 46100 Burjasot, Valencia, Spain.
Gil
M Luisa
ML
Departamento de Microbiología y Ecología, Universitat de València, Facultad de Ciencias Biológicas, Edificio de Investigación, C/Dr. Moliner 50, 46100 Burjasot, Valencia, Spain.
D000375:Aging; D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000097:blood / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004198:Disease Susceptibility; D005260:Female; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology; D025301:Hyphae / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014611:Vaccination
D000908:Antibodies, Fungal; D005657:Fungal Vaccines; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma