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

J-F Lauzon-Joset; N.M. Scott; K.T. Mincham; P.A. Stumbles; P.G. Holt; D.H. Strickland

doi:10.1093/infdis/jiy732

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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

Journal article

Peer reviewed

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

J-F Lauzon-Joset, N.M. Scott, K.T. Mincham, P.A. Stumbles, P.G. Holt and D.H. Strickland

The Journal of Infectious Diseases, Vol.219(11), pp.1823-1831

2018

DOI: 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.

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Title: 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
Authors/Creators: J-F Lauzon-Joset (Author/Creator) - The Kids Research Institute Australia
N.M. Scott (Author/Creator) - The Kids Research Institute Australia
K.T. Mincham (Author/Creator) - The Kids Research Institute Australia
P.A. Stumbles (Author/Creator) - Murdoch University
P.G. Holt (Author/Creator) - The Kids Research Institute Australia
D.H. Strickland (Author/Creator) - The Kids Research Institute Australia
Publication Details: The Journal of Infectious Diseases, Vol.219(11), pp.1823-1831
Publisher: Oxford University Press
Identifiers: 991005546350107891
Copyright: © 2018 The Author(s)
Murdoch Affiliation: School of Veterinary and Life Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.104 Virology - General; 1.104.126 Influenza
Web Of Science research areas: Immunology; Infectious Diseases; Microbiology
ESI research areas: Immunology