TY  - JOUR
A1  - Zoran, Tamara
A1  - Seelbinder, Bastian
A1  - White, Philip Lewis
A1  - Price, Jessica Sarah
A1  - Kraus, Sabrina
A1  - Kurzai, Oliver
A1  - Linde, Joerg
A1  - Häder, Antje
A1  - Loeffler, Claudia
A1  - Grigoleit, Goetz Ulrich
A1  - Einsele, Hermann
A1  - Panagiotou, Gianni
A1  - Loeffler, Juergen
A1  - Schäuble, Sascha
T1  - Molecular profiling reveals characteristic and decisive signatures in patients after allogeneic stem cell transplantation suffering from invasive pulmonary aspergillosis
JF  - Journal of Fungi
N2  - Despite available diagnostic tests and recent advances, diagnosis of pulmonary invasive aspergillosis (IPA) remains challenging. We performed a longitudinal case-control pilot study to identify host-specific, novel, and immune-relevant molecular candidates indicating IPA in patients post allogeneic stem cell transplantation (alloSCT). Supported by differential gene expression analysis of six relevant in vitro studies, we conducted RNA sequencing of three alloSCT patients categorized as probable IPA cases and their matched controls without Aspergillus infection (66 samples in total). We additionally performed immunoassay analysis for all patient samples to gain a multi-omics perspective. Profiling analysis suggested LGALS2, MMP1, IL-8, and caspase-3 as potential host molecular candidates indicating IPA in investigated alloSCT patients. MMP1, IL-8, and caspase-3 were evaluated further in alloSCT patients for their potential to differentiate possible IPA cases and patients suffering from COVID-19-associated pulmonary aspergillosis (CAPA) and appropriate control patients. Possible IPA cases showed differences in IL-8 and caspase-3 serum levels compared with matched controls. Furthermore, we observed significant differences in IL-8 and caspase-3 levels among CAPA patients compared with control patients. With our conceptual work, we demonstrate the potential value of considering the human immune response during Aspergillus infection to identify immune-relevant molecular candidates indicating IPA in alloSCT patients. These human host candidates together with already established fungal biomarkers might improve the accuracy of IPA diagnostic tools.
KW  - host response
KW  - invasive pulmonary aspergillosis
KW  - alloSCT patients
KW  - galectin-2
KW  - caspase-3
KW  - matrix metallopeptidase-1
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262105
SN  - 2309-608X
VL  - 8
IS  - 2
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  -