A B1a-natural IgG-neutrophil axis is impaired in viral- and steroid-associated aspergillosis.
Sci Transl Med
; 14(674): eabq6682, 2022 12 07.
Article
in English
| MEDLINE | ID: covidwho-2152884
ABSTRACT
The lung naturally resists Aspergillus fumigatus (Af) in healthy individuals, but multiple conditions can disrupt this resistance, leading to lethal invasive infections. Core processes of natural resistance and its breakdown are undefined. We investigated three distinct conditions predisposing to lethal aspergillosis-severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, influenza A viral pneumonia, and systemic corticosteroid use-in human patients and murine models. We found a conserved and essential coupling of innate B1a lymphocytes, Af-binding natural immunoglobulin G antibodies, and lung neutrophils. Failure of this axis concealed Af from neutrophils, allowing rapid fungal invasion and disease. Reconstituting the axis with immunoglobulin therapy reestablished resistance, thus representing a realistic pathway to repurpose currently available therapies. Together, we report a vital host resistance pathway that is responsible for protecting against life-threatening aspergillosis in the context of distinct susceptibilities.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19
/
Neutrophils
Type of study:
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
English
Journal:
Sci Transl Med
Journal subject:
Science
/
Medicine
Year:
2022
Document Type:
Article
Affiliation country:
Scitranslmed.abq6682
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