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

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Nat Commun


. 2021 Aug 16;12(1):4957.
doi: 10.1038/s41467-021-25220-3.
Offspring born to influenza A virus infected pregnant mice have increased susceptibility to viral and bacterial infections in early life


Henning Jacobsen ¹ , Kerstin Walendy-Gnirß ¹ , Nilgün Tekin-Bubenheim ¹ , Nancy Mounogou Kouassi ¹ , Isabel Ben-Batalla ^{2 3} , Nikolaus Berenbrok ^{2 3} , Martin Wolff ⁴ , Vinicius Pinho Dos Reis ¹ , Martin Zickler ¹ , Lucas Scholl ¹ , Annette Gries ¹ , Hanna Jania ¹ , Andreas Kloetgen ⁵ , Arne Düsedau ⁶ , Gundula Pilnitz-Stolze ⁷ , Aicha Jeridi ^{8 9} , Ali Önder Yildirim ^{8 9} , Helmut Fuchs ¹⁰ , Valerie Gailus-Durner ¹⁰ , Claudia Stoeger ¹⁰ , Martin Hrabe de Angelis ^{10 11 12} , Tatjana Manuylova ¹³ , Karin Klingel ¹³ , Fiona J Culley ¹⁴ , Jochen Behrends ¹⁵ , Sonja Loges ^{2 16 17} , Bianca Schneider ¹⁸ , Susanne Krauss-Etschmann ^{4 19} , Peter Openshaw ¹⁴ , Gülsah Gabriel ^{20 21 22}



Affiliations

• PMID: 34400653
• DOI: 10.1038/s41467-021-25220-3

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.