Journal
FRONTIERS IN IMMUNOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.00038
Keywords
signal transducer and activator of transcription 3 (STAT3); loss-of-function mutation; aspergillosis; innate/adaptive immunity; autosomal dominant hyper-19E syndrome (AD-HIES); Aspergillus; IgE; IgG
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Funding
- French national reference center for Primary Immunodeficiencies [CEREDIH, Hopital Necker-Enfants malades, Assistance Publique-Hopitaux (APHP) de Paris, Paris, France]
- Franco-Indian CEFIPRA [5403-1]
- ANR-DFG AfuINT grants
- Agence Nationale de la Recherche -Investissements d'Avenir program [ANR-10-IAHU-01]
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In humans, loss-of-function mutation in the Signal Transducer and Activator of Transcription 3 (STAT3) gene is frequently associated with susceptibility to bacterial as well as fungal infections including aspergillosis, although its pathogenesis remains largely unknown. In the present study, we investigated the immune responses obtained after stimulation with Aspergillus fumigatus in STAT3-deficient patients. A. fumigatus conidial killing efficiencies of both monocytes and neutrophils isolated from whole blood samples of STAT3-deficient patients were not different compared to those of healthy controls. After stimulation with A. fumigatus conidia, lower concentrations of adaptive cytokines (IFN-gamma, IL-17 and IL-22) were secreted by peripheral blood mononuclear cells from STAT3-deficient patients compared to those from healthy controls. Moreover, the frequency of IFN-gamma and IL-17 producing CD4+ T cells was lower in STAT3-deficient patients vs. healthy controls. Among the STAT3-deficient patients, those with aspergillosis showed further lower secretion of IFN-gamma upon stimulation of their PBMCs with A. fumigatus conidia compared to the patients without aspergillosis. Together, our study indicated that STAT3-deficiency leads to a defective adaptive immune response against A. fumigatus infection, particularly with a lower IFN-gamma and IL-17 responses in those with aspergillosis, suggesting potential therapeutic benefit of recombinant IFN-gamma in STAT3-deficient patients with aspergillosis.
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