In the recent study scientists of the Heinrich-Pette-Institute, Hamburg, and the University of Veterinary Medicine Hannover together with colleagues from the Imperial College London, the Helmholtz Zentrum München and the Research Center Borstel have employed a new animal model to investigate whether offspring of influenza A virus-infected mothers are more susceptible to other infections later in life. The results have now been published in "Nature Communications".
Influenza A viruses are some of the most prevalent viruses causing annual epidemics with up to five million severe cases every year. Although most healthy individuals only experience mild to moderate disease upon influenza virus infection, pregnant women are at increased risk of developing severe complications. It is known, that Influenza infection during pregnancy can affect the offspring in later life, and especially neurocognitive disorders are described. However, it remained unknown yet, if maternal influenza infection has adverse effects on immune responses in offspring, and can therefore affect health in later life.
In this study, the scientists established a new two-hit mouse model and could show that moderate influenza A infection during pregnancy increases the offspring's susceptibility to infection from other viruses as well as bacteria, especially early in life. Offspring born to influenza A virus infected mothers and offspring of control (PBS- or poly(I:C)-treated) mothers underwent a systemic phenotyping at the German Mouse Clinic, including lung physiology and function. It turned out, that they were stunted in growth and further investigations revealed, that they were more vulnerable to heterologous (second hit) infections of influenza B virus and Staphylococcus aureus (MRSA). Enhanced vulnerability to infection in neonates was associated with reduced haematopoetic development and immune responses.
The underlying mechanisms turned out to be multi-factorial, including maternal immune activation upon first hit, low birthweight of the offspring, and the failure of alveolar macrophages from offspring exposed to maternal influenza to clear second hit pathogens. In more detail, the key molecules that lead to this increased risk in the offspring of influenza-infected mothers are inflammatory cytokines in the mother's lungs after maternal immune activation (MIA). MIA correlated with increased IL-6, TNF, MCP-1, and IL-1ß levels in the lungs of influenza A virus-infected dams. The increased early life vulnerability of offspring to second hits correlated with low birthweight.
The new findings suggest that maternal influenza infection may impair immune ontogeny and increase susceptibility to early life infections of offspring, also emphasize the importance of measures that prevent maternal influenza.
Jacobsen H, Walendy-Gnirß K, Tekin-Bubenheim N, Kouassi NM, Ben-Batalla I, Berenbrok N, Wolff M, Dos Reis VP, Zickler M, Scholl L, Gries A, Jania H, Kloetgen A, Düsedau A, Pilnitz-Stolze G, Jeridi A, Yildirim AÖ, Fuchs H, Gailus-Durner V, Stoeger C, de Angelis MH, Manuylova T, Klingel K, Culley FJ, Behrends J, Loges S, Schneider B, Krauss-Etschmann S, Openshaw P, Gabriel G. Offspring born to influenza A virus infected pregnant mice have increased susceptibility to viral and bacterial infections in early life
Nat Commun. 2021 Aug 16;12(1):4957. doi: 10.1038/s41467-021-25220-3.