Interaction of radiolabeled antibodies with fungal cells and components of the immune system in vitro and during radioimmunotherapy for experimental fungal infection

Ekaterina Dadachova, Ruth A. Bryan, Christos Apostolidis, Alfred Morgenstern, Tong Zhang, Tiffany Moadel, Marcela Torres, Xianchun Huang, Ekaterina Revskaya, Arturo Casadevall

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Background. The usefulness of radioimmunotherapy (RIT) for infectious diseases was recently demonstrated for several fungal and bacterial infections, but the mechanisms by which RIT is effective against microbes are uncertain. Methods. We investigated the interaction between polysaccharide capsule-binding 18B7 monoclonal antibodies (MAbs) labeled with α-emitter 213Bi and Cryptococcus neoformans cells as well as between 213Bi-18B7 and components of immune system, both in vitro and in vivo. Results. For 213Bi-18B7, the microbicidal effect was predominantly due to "direct-hit" killing, with some contribution from the "crossfire" effect. The efficacy of cell killing correlated with the binding capacity of the MAb to the capsule and was dependent on the MAb isotype. RIT also promoted the apoptosis-like death of fungal cells. Cooperation was observed in vitro between the antifungal activity of macrophages and RIT, suggesting the potential for synergistic action in vivo. RIT was associated with changes in concentration of the cytokines interleukin (IL)-2, IL-4, IL-10, tumor necrosis factor-α, and interferon-γ, suggesting that the therapeutic effects of RIT may result from changes in the inflammatory response. Conclusions. The present results suggest that the antimicrobial efficacy of RIT involves killing through promotion of fungal cell apoptosis-like death, reduction in yeast capsule size, cooperation with macrophages, and modulation of the inflammatory response.

Original languageEnglish (US)
Pages (from-to)1427-1436
Number of pages10
JournalJournal of Infectious Diseases
Volume193
Issue number10
DOIs
StatePublished - May 15 2006

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Dadachova, E., Bryan, R. A., Apostolidis, C., Morgenstern, A., Zhang, T., Moadel, T., Torres, M., Huang, X., Revskaya, E., & Casadevall, A. (2006). Interaction of radiolabeled antibodies with fungal cells and components of the immune system in vitro and during radioimmunotherapy for experimental fungal infection. Journal of Infectious Diseases, 193(10), 1427-1436. https://doi.org/10.1086/503369