Offspring born to influenza A virus infected pregnant mice have increased susceptibility to viral and bacterial infections in early life

Henning Jacobsen, Kerstin Walendy-Gnirß, Nilgün Tekin-Bubenheim, Nancy Mounogou Kouassi, Isabel Ben-Batalla, Nikolaus Berenbrok, Martin Wolff, Vinicius Pinho Reis, Martin Zickler, Lucas Scholl, Annette Gries, Hanna Jania, Andreas Kloetgen, Arne Düsedau, Gundula Pilnitz-Stolze, Aicha Jeridi, Ali Önder Yildirim, Helmut Fuchs, Valerie Gailus-Durner, Claudia Stoeger, Martin Hrabe Angelis, Tatjana Manuylova, Karin Klingel, Fiona J. Culley, Jochen Behrends, Sonja Loges, Bianca Schneider, Susanne Krauss-Etschmann, Peter Openshaw and Gülsah Gabriel ()
Additional contact information
Henning Jacobsen: Leibniz Institute for Experimental Virology
Kerstin Walendy-Gnirß: Leibniz Institute for Experimental Virology
Nilgün Tekin-Bubenheim: Leibniz Institute for Experimental Virology
Nancy Mounogou Kouassi: Leibniz Institute for Experimental Virology
Isabel Ben-Batalla: University Medical Center Hamburg-Eppendorf
Nikolaus Berenbrok: University Medical Center Hamburg-Eppendorf
Martin Wolff: Member of the German Center for Lung Research (DZL)
Vinicius Pinho Reis: Leibniz Institute for Experimental Virology
Martin Zickler: Leibniz Institute for Experimental Virology
Lucas Scholl: Leibniz Institute for Experimental Virology
Annette Gries: Leibniz Institute for Experimental Virology
Hanna Jania: Leibniz Institute for Experimental Virology
Andreas Kloetgen: Helmholtz Centre for Infection Research
Arne Düsedau: Leibniz-Institute for Experimental Virology
Gundula Pilnitz-Stolze: Leibniz-Institute for Experimental Virology
Aicha Jeridi: Helmholtz Center Munich, German Research Center for Environmental Health
Ali Önder Yildirim: Helmholtz Center Munich, German Research Center for Environmental Health
Helmut Fuchs: Helmholtz Center Munich, German Research Center for Environmental Health
Valerie Gailus-Durner: Helmholtz Center Munich, German Research Center for Environmental Health
Claudia Stoeger: Helmholtz Center Munich, German Research Center for Environmental Health
Martin Hrabe Angelis: Helmholtz Center Munich, German Research Center for Environmental Health
Tatjana Manuylova: University Hospital Tübingen
Karin Klingel: University Hospital Tübingen
Fiona J. Culley: Imperial College London
Jochen Behrends: Research Center Borstel, Leibniz Lung Center
Sonja Loges: University Medical Center Hamburg-Eppendorf
Bianca Schneider: Research Center Borstel, Leibniz Lung Center
Susanne Krauss-Etschmann: Member of the German Center for Lung Research (DZL)
Peter Openshaw: Imperial College London
Gülsah Gabriel: Leibniz Institute for Experimental Virology

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Influenza during pregnancy can affect the health of offspring in later life, among which neurocognitive disorders are among the best described. Here, we investigate whether maternal influenza infection has adverse effects on immune responses in offspring. We establish a two-hit mouse model to study the effect of maternal influenza A virus infection (first hit) on vulnerability of offspring to heterologous infections (second hit) in later life. Offspring born to influenza A virus infected mothers are stunted in growth and more vulnerable to heterologous infections (influenza B virus and MRSA) than those born to PBS- or poly(I:C)-treated mothers. Enhanced vulnerability to infection in neonates is associated with reduced haematopoetic development and immune responses. In particular, alveolar macrophages of offspring exposed to maternal influenza have reduced capacity to clear second hit pathogens. This impaired pathogen clearance is partially reversed by adoptive transfer of alveolar macrophages from healthy offspring born to uninfected dams. These findings suggest that maternal influenza infection may impair immune ontogeny and increase susceptibility to early life infections of offspring.

Date: 2021
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DOI: 10.1038/s41467-021-25220-3

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