Mucorales-specific T cells in patients with hematologic malignancies

Leonardo Potenza, Daniela Vallerini, Patrizia Barozzi, Giovanni Riva, Andrea Gilioli, Fabio Forghieri, Anna Candoni, Simone Cesaro, Chiara Quadrelli, Johan Maertens, Giulio Rossi, Monica Morselli, Mauro Codeluppi, Cristina Mussini, Elisabetta Colaci, Andrea Messerotti, Ambra Paolini, Monica Maccaferri, Valeria Fantuzzi, Cinzia Del GiovaneAlessandro Stefani, Uliano Morandi, Rossana Maffei, Roberto Marasca, Franco Narni, Renato Fanin, Patrizia Comoli, Luigina Romani, Anne Beauvais, Pier Luigi Viale, Jean Paul Latgè, Russell E. Lewis, Mario Luppi

Research output: Contribution to journalArticle

Abstract

Background: Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. Methods and Findings: By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during highdose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD):2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. Conclusions: Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.

Original languageEnglish
Article numbere0149108
JournalPLoS One
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

    Fingerprint

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Potenza, L., Vallerini, D., Barozzi, P., Riva, G., Gilioli, A., Forghieri, F., Candoni, A., Cesaro, S., Quadrelli, C., Maertens, J., Rossi, G., Morselli, M., Codeluppi, M., Mussini, C., Colaci, E., Messerotti, A., Paolini, A., Maccaferri, M., Fantuzzi, V., ... Luppi, M. (2016). Mucorales-specific T cells in patients with hematologic malignancies. PLoS One, 11(2), [e0149108]. https://doi.org/10.1371/journal.pone.0149108