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A B1a-natural IgG-neutrophil axis is impaired in viral- and steroid-associated aspergillosis.
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.
Afiliação
  • Sarden N; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Sinha S; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Potts KG; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada.
  • Pernet E; Arnie Charbonneau Cancer Institute, Departments of Biochemistry and Molecular Biology and Microbiology, Immunology, and Infectious Diseases, University of Calgary, Calgary, AB T2N 4Z6, Canada.
  • Hiroki CH; Meakins-Christie Laboratories, Departments of Medicine and Pathology, McGill International TB Centre, McGill University, Montreal, QC H4A 3JI, Canada.
  • Hassanabad MF; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
  • Nguyen AP; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Lou Y; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Farias R; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Winston BW; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Bromley A; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Snarr BD; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Zucoloto AZ; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Andonegui G; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Muruve DA; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • McDonald B; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Sheppard DC; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Mahoney DJ; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Divangahi M; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Rosin N; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
  • Biernaskie J; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
  • Yipp BG; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
Sci Transl Med ; 14(674): eabq6682, 2022 12 07.
Article em En | MEDLINE | ID: mdl-36475902
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: COVID-19 / Neutrófilos Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: COVID-19 / Neutrófilos Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article