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Colombo SAP, Hashad R, Denning DW, et al. Defective interferon-gamma production is common in chronic pulmonary aspergillosis. J Infect Dis. 2021;doi: 10.1093/infdis/jiab583.
Colombo, S. A. P., Hashad, R., Denning, D. W., Kumararatne, D. S., Ceron-Gutierrez, L., Barcenas-Morales, G., MacDonald, A. S., Harris, C., Doffinger, R., & Kosmidis, C. (2021). Defective interferon-gamma production is common in chronic pulmonary aspergillosis. The Journal of infectious diseases, . https://doi.org/10.1093/infdis/jiab583
Colombo, Stefano A P, et al. "Defective interferon-gamma production is common in chronic pulmonary aspergillosis." The Journal of infectious diseases vol. (2021). doi: https://doi.org/10.1093/infdis/jiab583
Colombo SAP, Hashad R, Denning DW, Kumararatne DS, Ceron-Gutierrez L, Barcenas-Morales G, MacDonald AS, Harris C, Doffinger R, Kosmidis C. Defective interferon-gamma production is common in chronic pulmonary aspergillosis. J Infect Dis. 2021 Nov 29; doi: 10.1093/infdis/jiab583. Epub 2021 Nov 29. PMID: 34850023.
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J Infect Dis. 2021 Nov 29; doi: 10.1093/infdis/jiab583. Epub 2021 Nov 29.

Defective interferon-gamma production is common in chronic pulmonary aspergillosis.

The Journal of infectious diseases

Stefano A P Colombo, Rola Hashad, David W Denning, Dinakantha S Kumararatne, Lourdes Ceron-Gutierrez, Gabriela Barcenas-Morales, Andrew S MacDonald, Chris Harris, Rainer Doffinger, Chris Kosmidis

Affiliations

  1. Lydia Becker Institute of Immunology and Inflammation, Manchester Collaborative Centre for Inflammation Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
  2. Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, UK.
  3. Department of Medical Microbiology and Immunology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
  4. Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, UK.
  5. Department of Clinical Biochemistry and Immunology, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, UK.
  6. Laboratorio 2 de Inmunologia, FES-Cuautitlan, UNAM, Mexico.
  7. National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.

PMID: 34850023 DOI: 10.1093/infdis/jiab583

Abstract

BACKGROUND: Immune defects in chronic pulmonary aspergillosis (CPA) are poorly characterised. We compared peripheral blood cytokine profiles in patients with CPA vs healthy controls and explored the relationship with disease severity.

METHODS: Interferon-gamma (IFNγ), IL-17, TNFα, IL-6, IL-12 and IL-10 were measured after in vitro stimulation of whole blood with lipopolysaccharide (LPS), phytohaemagglutinin (PHA), β-glucan, zymosan (ZYM), IL-12 or IL-18, and combinations. Clinical parameters and mortality were correlated with cytokine production.

RESULTS: Cytokine profiles were evaluated in 133 patients (57.1% male, mean age 61 years). In comparison to controls, patients with CPA had significantly reduced production of IFNγ in response to stimulation with β-glucan+IL-12 (312 vs 988 pg/ml), LPS+IL-12 (252 vs 1033 pg/ml), ZYM+IL-12 (996 vs 2347 pg/ml), and IL-18+IL-12 (7193 vs 12330 pg/ml). Age >60 (p=0.05, HR 1.71, 95%CI 1.00-2.91) and COPD (p=0.039, HR 1.69, 95%CI 1.03-2.78) were associated with worse survival, whereas high IFNγ production in response to beta-glucan+IL-12 stimulation (p=0.026, HR 0.48, 95%CI 0.25-0.92) was associated with reduced mortality.

CONCLUSION: Patients with CPA show impaired IFNγ production in peripheral blood in response to stimuli. Defective IFNγ production ability correlates with worse outcomes. Immunotherapy with IFNγ could be beneficial for patients showing impaired IFNγ production in CPA.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Keywords: Chronic pulmonary aspergillosis; IL-17A; cytokines; immunotherapy; interferon-gamma; pathogenesis

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