Chronic Disseminated Candidiasis During Hematological Malignancies: An Immune Reconstitution Inflammatory Syndrome With Expansion of Pathogen-Specific T Helper Type 1 Cells.
immune reconstitution inflammatory syndrome
interferon gamma
invasive candidiasis
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
11 05 2020
11 05 2020
Historique:
received:
17
12
2019
accepted:
23
12
2019
pubmed:
28
12
2019
medline:
1
4
2021
entrez:
28
12
2019
Statut:
ppublish
Résumé
Chronic disseminated candidiasis (CDC) is a rare disease that mostly occurs after chemotherapy-induced prolonged neutropenia in patients with hematological malignancies. It is believed to ensue from Candida colonization, breach of the intestinal epithelial barrier, and venous translocation to organs. Fungal blood or liver biopsy cultures are generally negative, suggesting the absence of an ongoing invasive fungal disease. To unravel the contribution of the immune system to CDC pathogenesis, we undertook a prospective multicentric exploratory study in 44 CDC patients at diagnosis and 44 matched controls. Analysis of Candida-specific T-cell responses using enzyme-linked immunospot assays revealed higher numbers of interferon (IFN)γ-producing T cells reactive to mp65 or candidin in 27 CDC cases compared with 33 controls. Increased plasma levels of soluble CD25, interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and IL-10 and lower levels of IL-2 were observed in CDC patients versus controls. Neutrophilia and higher levels of CD4 and CD8 T-cell activation were found in CDC patients as well as increased proportions of CXCR3-expressing TCRγδ +Vδ2+ cells. The expansion of Candida-specific IFNγ-producing T cells together with features of T-cell activation and systemic inflammation identified here support the view that CDC belongs to the broad spectrum of fungal-associated immune reconstitution inflammatory syndromes.
Sections du résumé
BACKGROUND
Chronic disseminated candidiasis (CDC) is a rare disease that mostly occurs after chemotherapy-induced prolonged neutropenia in patients with hematological malignancies. It is believed to ensue from Candida colonization, breach of the intestinal epithelial barrier, and venous translocation to organs. Fungal blood or liver biopsy cultures are generally negative, suggesting the absence of an ongoing invasive fungal disease.
METHODS
To unravel the contribution of the immune system to CDC pathogenesis, we undertook a prospective multicentric exploratory study in 44 CDC patients at diagnosis and 44 matched controls.
RESULTS
Analysis of Candida-specific T-cell responses using enzyme-linked immunospot assays revealed higher numbers of interferon (IFN)γ-producing T cells reactive to mp65 or candidin in 27 CDC cases compared with 33 controls. Increased plasma levels of soluble CD25, interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and IL-10 and lower levels of IL-2 were observed in CDC patients versus controls. Neutrophilia and higher levels of CD4 and CD8 T-cell activation were found in CDC patients as well as increased proportions of CXCR3-expressing TCRγδ +Vδ2+ cells.
CONCLUSIONS
The expansion of Candida-specific IFNγ-producing T cells together with features of T-cell activation and systemic inflammation identified here support the view that CDC belongs to the broad spectrum of fungal-associated immune reconstitution inflammatory syndromes.
Identifiants
pubmed: 31879764
pii: 5687810
doi: 10.1093/infdis/jiz688
doi:
Substances chimiques
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1907-1916Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.