TY  - JOUR
A1  - Lauruschkat, Chris D.
A1  - Etter, Sonja
A1  - Schnack, Elisabeth
A1  - Ebel, Frank
A1  - Schäuble, Sascha
A1  - Page, Lukas
A1  - Rümens, Dana
A1  - Dragan, Mariola
A1  - Schlegel, Nicolas
A1  - Panagiotou, Gianni
A1  - Kniemeyer, Olaf
A1  - Brakhage, Axel A.
A1  - Einsele, Hermann
A1  - Wurster, Sebastian
A1  - Loeffler, Juergen
T1  - Chronic occupational mold exposure drives expansion of Aspergillus-reactive type 1 and type 2 T-helper cell responses
JF  - Journal of Fungi
N2  - Occupational mold exposure can lead to Aspergillus-associated allergic diseases including asthma and hypersensitivity pneumonitis. Elevated IL-17 levels or disbalanced T-helper (Th) cell expansion were previously linked to Aspergillus-associated allergic diseases, whereas alterations to the Th cell repertoire in healthy occupationally exposed subjects are scarcely studied. Therefore, we employed functional immunoassays to compare Th cell responses to A. fumigatus antigens in organic farmers, a cohort frequently exposed to environmental molds, and non-occupationally exposed controls. Organic farmers harbored significantly higher A. fumigatus-specific Th-cell frequencies than controls, with comparable expansion of Th1- and Th2-cell frequencies but only slightly elevated Th17-cell frequencies. Accordingly, Aspergillus antigen-induced Th1 and Th2 cytokine levels were strongly elevated, whereas induction of IL-17A was minimal. Additionally, increased levels of some innate immune cell-derived cytokines were found in samples from organic farmers. Antigen-induced cytokine release combined with Aspergillus-specific Th-cell frequencies resulted in high classification accuracy between organic farmers and controls. Aspf22, CatB, and CipC elicited the strongest differences in Th1 and Th2 responses between the two cohorts, suggesting these antigens as potential candidates for future bio-effect monitoring approaches. Overall, we found that occupationally exposed agricultural workers display a largely balanced co-expansion of Th1 and Th2 immunity with only minor changes in Th17 responses.
KW  - mold exposure
KW  - immunoassay
KW  - biomarker
KW  - Aspergillus
KW  - cytokines
KW  - inflammation
KW  - adaptive immunity
KW  - hypersensitivity
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245202
SN  - 2309-608X
VL  - 7
IS  - 9
ER  - 
TY  - JOUR
A1  - Tappe, Beeke
A1  - Lauruschkat, Chris D.
A1  - Strobel, Lea
A1  - Pantaleón García, Jezreel
A1  - Kurzai, Oliver
A1  - Rebhan, Silke
A1  - Kraus, Sabrina
A1  - Pfeuffer-Jovic, Elena
A1  - Bussemer, Lydia
A1  - Possler, Lotte
A1  - Held, Matthias
A1  - Hünniger, Kerstin
A1  - Kniemeyer, Olaf
A1  - Schäuble, Sascha
A1  - Brakhage, Axel A.
A1  - Panagiotou, Gianni
A1  - White, P. Lewis
A1  - Einsele, Hermann
A1  - Löffler, Jürgen
A1  - Wurster, Sebastian
T1  - COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
JF  - Frontiers in Immunology
N2  - Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus- and R. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients.
KW  - COVID-19
KW  - immune impairment
KW  - T cells
KW  - granulocytes
KW  - Aspergillus
KW  - Rhizopus
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283558
SN  - 1664-3224
VL  - 13
ER  -