Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Géraldine Engels, Alexandra Maximiliane Hierweger, Julia Hoffmann, René Thieme, Swantje Thiele, Stephanie Bertram, Carola Dreier, Patricia Resa-Infante, Henning Jacobsen, Kristin Thiele, Malik Alawi, Daniela Indenbirken, Adam Grundhoff, Svenja Siebels, Nicole Fischer, Violeta Stojanovska, Damián Muzzio, Federico Jensen, Khalil Karimi, Hans-Willi Mittrücker, Petra Clara Arck, Gülsah Gabriel
Pregnant women are at high risk for severe influenza disease outcomes, yet insights into the underlying mechanisms are limited. Here, we present models of H1N1 infection in syngenic and allogenic pregnant mice; infection in the latter mirrors the severe course of 2009 pandemic influenza in pregnant women. We found that the anti-viral immune response in the pregnant host was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8⁺ T cells into the lung. The multi-faceted failure to mount an anti-viral response in allogenic pregnant mice resulted in a less stringent selective environment that promoted the emergence of 2009 H1N1 virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity. These insights underscore the importance of influenza vaccination compliance in pregnant women and may open novel therapeutic avenues.

Graphical abstract

Teaser

Pregnant women are at highest risk during influenza pandemics. Engels and colleagues present influenza infection models in mice and show that the immune response, which is tailored to accommodate the semiallogenic fetus, restricts the anti-viral immune response during gestation. Under these conditions, highly pathogenic virus variants can emerge.


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