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Pregnancy induces a Steady-State shift in alveolar macrophage M1/M2 phenotype that is associated with a heightened severity of influenza virus infection: mechanistic insight using mouse models

Lauzon-Joset, J-F, Scott, N.M., Mincham, K.T., Stumbles, P.A., Holt, P.G. and Strickland, D.H. (2018) Pregnancy induces a Steady-State shift in alveolar macrophage M1/M2 phenotype that is associated with a heightened severity of influenza virus infection: mechanistic insight using mouse models. The Journal of Infectious Diseases, 219 (11). pp. 1823-1831.

Link to Published Version: https://doi.org/10.1093/infdis/jiy732
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Abstract

Background
Influenza virus infection during pregnancy is associated with enhanced disease severity. However, the underlying mechanisms are still not fully understood. We hypothesized that normal alveolar macrophage (AM) functions, which are central to maintaining lung immune homeostasis, are altered during pregnancy and that this dysregulation contributes to the increased inflammatory response to influenza virus infection.

Methods
Time-mated BALB/c mice were infected with a low dose of H1N1 influenza A virus at gestation day 9.5. Inflammatory cells in bronchoalveolar lavage (BAL) fluid were assessed by flow cytometry.

Results
Our findings confirm previous reports of increased severity of influenza virus infection in pregnant mice. The heightened inflammatory response detected in BAL fluid from infected pregnant mice was characterized by neutrophil-rich inflammation with concomitantly reduced numbers of AM, which were slower to return to baseline counts, compared with nonpregnant infected mice. The increased infection severity and inflammatory responses to influenza during pregnancy were associated with a pregnancy-induced shift in AM phenotype at homeostatic baseline, from the M1 (ie, classical activation) state toward the M2 (ie, alternative activation) state, as evidence by increased expression of CD301 and reduced levels of CCR7.

Conclusion
These results show that pregnancy is associated with an alternatively activated phenotype of AM before infection, which may contribute to heightened disease severity.

Item Type: Journal Article
Murdoch Affiliation: School of Veterinary and Life Sciences
Publisher: Oxford University Press
Copyright: © 2018 The Author(s)
URI: http://researchrepository.murdoch.edu.au/id/eprint/51109
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