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J Infect Dis. 2018 Dec 21. doi: 10.1093/infdis/jiy732. [Epub ahead of print]
Pregnancy induces a steady-state shift in alveolar macrophage M1/M2 phenotype that is associated with a heightened severity of Influenza infection: mechanistic insight using mouse models.
Lauzon-Joset JF1, Scott NM1, Mincham KT1,2, Stumbles PA1,3, Holt PG1, Strickland DH1.
Author information
Abstract
Background:
Influenza infection during pregnancy is associated with enhanced disease severity, however the underlying mechanisms are still not fully understood. We hypothesised 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 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) were assessed by flow cytometry.
Results:
Our findings confirm previous reports of increased severity of Influenza infection in pregnant mice. The heightened BAL inflammatory response in infected pregnant mice was characterised by a neutrophil rich inflammation with concomitant reduced numbers of AM, which were slower to return to baseline compared to non-pregnant 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 a M1 towards the M2 (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.
PMID: 30576502 DOI: 10.1093/infdis/jiy732
Pregnancy induces a steady-state shift in alveolar macrophage M1/M2 phenotype that is associated with a heightened severity of Influenza infection: mechanistic insight using mouse models.
Lauzon-Joset JF1, Scott NM1, Mincham KT1,2, Stumbles PA1,3, Holt PG1, Strickland DH1.
Author information
Abstract
Background:
Influenza infection during pregnancy is associated with enhanced disease severity, however the underlying mechanisms are still not fully understood. We hypothesised 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 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) were assessed by flow cytometry.
Results:
Our findings confirm previous reports of increased severity of Influenza infection in pregnant mice. The heightened BAL inflammatory response in infected pregnant mice was characterised by a neutrophil rich inflammation with concomitant reduced numbers of AM, which were slower to return to baseline compared to non-pregnant 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 a M1 towards the M2 (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.
PMID: 30576502 DOI: 10.1093/infdis/jiy732