1887

Abstract

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 . Aged C57BL/6 mice that were experimentally infected intravenously had a significantly impaired survival and a higher tissue fungal burden compared with young mice. production of tumour necrosis factor (TNF)- by macrophages from aged mice in response to yeast cells and hyphae of was significantly lower than production by macrophages from young mice. production of cytokines, such as TNF- and gamma interferon (IFN-), by antigen-stimulated splenocytes from mice intravenously infected with 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--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 -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 and are more susceptible to systemic primary candidiasis.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.46740-0
2006-12-01
2019-11-20
Loading full text...

Full text loading...

/deliver/fulltext/jmm/55/12/1649.html?itemId=/content/journal/jmm/10.1099/jmm.0.46740-0&mimeType=html&fmt=ahah

References

  1. Boehmer, E. D., Goral, J., Faunce, D. E. & Kovacs, E. J. ( 2004; ). Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression. J Leukoc Biol 75, 342–349.
    [Google Scholar]
  2. Boehmer, E. D., Meehan, M. J., Cutro, B. T. & Kovacs, E. J. ( 2005; ). Aging negatively skews macrophage TLR2- and TLR4-mediated pro-inflammatory responses without affecting the IL-2-stimulated pathway. Mech Ageing Dev 126, 1305–1313.[CrossRef]
    [Google Scholar]
  3. Bromuro, C., Torosantucci, A., Chiani, P., Conti, S., Polonelli, L. & Cassone, A. ( 2002; ). Interplay between protective and inhibitory antibodies dictates the outcome of experimentally disseminated candidiasis in recipients of Candida albicans vaccine. Infect Immun 70, 5462–5470.[CrossRef]
    [Google Scholar]
  4. Calderone, R. A. ( 2001; ). Candida and Candidiasis. New York: American Society for Microbiology.
  5. Effros, R. B. ( 2001; ). Ageing and the immune system. Novartis Found Symp 235, 130–139.
    [Google Scholar]
  6. Garber, G. ( 2001; ). An overview of fungal infections. Drugs 61, 1–12.
    [Google Scholar]
  7. Gil, M. L. & Gozalbo, D. ( 2006; ). TLR2, but not TLR4, triggers cytokine production by murine cells in response to Candida albicans yeasts and hyphae. Microbes Infect 8, 2299–2304.[CrossRef]
    [Google Scholar]
  8. Gil-Navarro, I., Gil, M. L., Casanova, M., O'Connor, J. E., Martínez, J. P. & Gozalbo, D. ( 1997; ). The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase of Candida albicans is a surface antigen. J Bacteriol 179, 4992–4999.
    [Google Scholar]
  9. Ginaldi, L., Loreto, M. F., Corsi, M. P., Modesti, M. & De Martinis, M. ( 2001; ). Immunosenescence and infectious diseases. Microbes Infect 3, 851–857.[CrossRef]
    [Google Scholar]
  10. Gozalbo, D., Gil-Navarro, I., Azorín, I., Renau-Piqueras, J., Martínez, J. P. & Gil, M. L. ( 1998; ). The cell wall-associated glyceraldehyde-3-phosphate dehydrogenase of Candida albicans is also a fibronectin and laminin binding protein. Infect Immun 66, 2052–2059.
    [Google Scholar]
  11. Kauffman, C. A. ( 2001; ). Fungal infections in older adults. Clin Infect Dis 33, 550–555.[CrossRef]
    [Google Scholar]
  12. Matthews, R. C., Rigg, G., Hodgetts, S., Carter, T., Chapman, C., Gregory, C., Illidge, C. & Burnie, J. ( 2003; ). Preclinical assessment of the efficacy of Mycograb, a human recombinant antibody against fungal HSP90. Antimicrobial Agents Chemother 47, 2208–2216.[CrossRef]
    [Google Scholar]
  13. McGlauchlen, K. S. & Vogel, L. A. ( 2003; ). Ineffective humoral immunity in the elderly. Microbes Infect 5, 1279–1284.[CrossRef]
    [Google Scholar]
  14. Montagnoli, C., Sandini, S., Bacci, A., Romani, L. & La Valle, R. ( 2004; ). Immunogenicity and protective effect of recombinant enolase of Candida albicans in a murine model of systemic candidiasis. Med Mycol 42, 319–324.[CrossRef]
    [Google Scholar]
  15. Netea, M. G., van Tits, L. J. H., Curfs, J. H. A. J., Amiot, F., Meis, J. F. G. M., van der Meer, J. W. M. & Kullberg, B. J. ( 1999; ). Increased susceptibility of TNF-α lymphotoxin-α double knockout mice to systemic candidiasis through impaired recruitment of neutrophils and phagocytosis of Candida albicans. J Immunol 163, 1498–1505.
    [Google Scholar]
  16. Nucci, M., Colombo, A. L., Silveira, F., Richtmann, R., Salomão, R., Branchini, M. L. & Spector, N. ( 1998; ). Risk factors for death in patients with candidemia. Infect Control Hosp Epidemiol 11, 846–850.
    [Google Scholar]
  17. Plackett, T. P., Boehmer, E. D., Faunce, D. E. & Kovacs, E. J. ( 2004; ). Aging and innate immune cells. J Leukoc Biol 76, 291–299.[CrossRef]
    [Google Scholar]
  18. Renshaw, M., Rockwell, J., Engleman, C., Gewirtz, A., Katz, J. & Sambhara, S. ( 2002; ). Cutting edge: impaired Toll-like receptor expression and function in aging. J Immunol 169, 4697–4701.[CrossRef]
    [Google Scholar]
  19. Romani, L. ( 2004; ). Immunity to fungal infections. Nat Rev Immunol 4, 1–23.[CrossRef]
    [Google Scholar]
  20. Romani, L., Mocci, S., Bietta, C., Lanfaloni, L., Puccetti, P. & Bistoni, F. ( 1991; ). Th1 and Th2 cytokine secretion patterns in murine candidiasis: association of Th1 responses with acquired resistance. Infect Immun 59, 4647–4654.
    [Google Scholar]
  21. Steinshamn, S., Bemelmans, M. H. A., Van Tits, L. H. J., Bergh, K., Buurman, W. A. & Waage, A. ( 1996; ). TNF receptors in murine Candida albicans infection: evidence for an important role of TNF receptor p55 in antifungal defense. J Immunol 157, 2155–2159.
    [Google Scholar]
  22. Torosantucci, A., Bromuro, C., Chiani, P. & 9 other authors ( 2005; ). A novel glyco-conjugate vaccine against fungi pathogens. J Exp Med 202, 597–606.[CrossRef]
    [Google Scholar]
  23. Vilanova, M., Teixeira, L., Caramalho, I. & 7 other authors ( 2004; ). Protection against systemic candidiasis in mice immunized with secreted aspartic proteinase 2. Immunology 111, 334–342.[CrossRef]
    [Google Scholar]
  24. Villamón, E., Gozalbo, D., Roig, P., Murciano, C., O'Connor, J. E., Fradelizi, D. & Gil, M. L. ( 2004a; ). Myeloid differentiation factor 88 (MyD88) is required for murine resistance to Candida albicans and is critically involved in Candida-induced production of cytokines. Eur Cytokine Netw 15, 263–271.
    [Google Scholar]
  25. Villamón, E., Gozalbo, D., Roig, P., O'Connor, J. E., Fradelizi, D. & Gil, M. L. ( 2004b; ). Toll-like receptor-2 is essential in murine defenses against Candida albicans infections. Microbes Infect 6, 1–7.[CrossRef]
    [Google Scholar]
  26. Villamón, E., Gozalbo, D., Roig, P., O'Connor, J. E., Ferrandiz, M. L., Fradelizi, D. & Gil, M. L. ( 2004c; ). Toll-like receptor 2 is dispensable for acquired host immune resistance to Candida albicans in a murine model of disseminated candidiasis. Microbes Infect 6, 542–548.[CrossRef]
    [Google Scholar]
  27. Zhang, M. X., Bohlman, M. C., Itatani, C., Burton, D. R., Parren, P. W. H. I., St Jeor, S. C. & Kozel, T. R. ( 2006; ). Human recombinant antimannan immunoglobulin G1 antibody confers resistance to hematogenously disseminated candidiasis in mice. Infect Immun 74, 362–369.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.46740-0
Loading
/content/journal/jmm/10.1099/jmm.0.46740-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error