Science translational medicine · 2022
A B1a-natural IgG-neutrophil axis is impaired in viral- and steroid-associated aspergillosis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Sarden Nicole, Sinha Sarthak, Potts Kyle G, Pernet Erwan, Hiroki Carlos H, Hassanabad Mortaza F, Nguyen Angela P, Lou Yuefei, Farias Raquel, Winston Brent W, Bromley Amy, Snarr Brendan D, Zucoloto Amanda Z, Andonegui Graciela, Muruve Daniel A, McDonald Braedon, Sheppard Donald C, Mahoney Douglas J, Divangahi Maziar, Rosin Nicole, Biernaskie Jeff, Yipp Bryan G
Аннотация
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.