tetano
Editor, Senior Moderator
Brain Behav Immun
. 2021 May 11;S0889-1591(21)00185-9.
doi: 10.1016/j.bbi.2021.05.004. Online ahead of print.
Moderately pathogenic maternal influenza A virus infection disrupts placental integrity but spares the fetal brain
Adrienne M Antonson[SUP] 1 [/SUP], Adam D Kenney[SUP] 2 [/SUP], Helen J Chen[SUP] 3 [/SUP], Kara N Corps[SUP] 4 [/SUP], Jacob S Yount[SUP] 2 [/SUP], Tamar L Gur[SUP] 5 [/SUP]
Affiliations
Abstract
Maternal infection during pregnancy is a known risk factor for offspring mental health disorders. Animal models of maternal immune activation (MIA) have implicated specific cellular and molecular etiologies of psychiatric illness, but most rely on pathogen mimetics. Here, we developed a mouse model of live H3N2 influenza A virus (IAV) infection during pregnancy that induces a robust inflammatory response but is sublethal to both dams and offspring. We observed classic indicators of lung inflammation and severely diminished weight gain in IAV-infected dams. This was accompanied by immune cell infiltration in the placenta and partial breakdown of placental integrity. However, indications of fetal neuroinflammation were absent. Further hallmarks of mimetic-induced MIA, including enhanced circulating maternal IL-17A, were also absent. Respiratory IAV infection did result in an upregulation in intestinal expression of transcription factor ROR?t, master regulator of a subset of T lymphocytes, T[SUB]H[/SUB]17 cells, which are heavily implicated in MIA-induced etiologies. Nonetheless, subsequent augmentation in IL-17A production and concomitant overt intestinal injury was not evident. Our results suggest that mild or moderately pathogenic IAV infection during pregnancy does not inflame the developing fetal brain, and highlight the importance of live pathogen infection models for the study of MIA.
Keywords: T helper 17 cells; fetal development; fetal neuroinflammation; gestational infection; infection during pregnancy; influenza A virus; influenza infection; maternal immune activation; maternal inflammation; maternal viral infection.
. 2021 May 11;S0889-1591(21)00185-9.
doi: 10.1016/j.bbi.2021.05.004. Online ahead of print.
Moderately pathogenic maternal influenza A virus infection disrupts placental integrity but spares the fetal brain
Adrienne M Antonson[SUP] 1 [/SUP], Adam D Kenney[SUP] 2 [/SUP], Helen J Chen[SUP] 3 [/SUP], Kara N Corps[SUP] 4 [/SUP], Jacob S Yount[SUP] 2 [/SUP], Tamar L Gur[SUP] 5 [/SUP]
Affiliations
- PMID: 33989741
- DOI: 10.1016/j.bbi.2021.05.004
Abstract
Maternal infection during pregnancy is a known risk factor for offspring mental health disorders. Animal models of maternal immune activation (MIA) have implicated specific cellular and molecular etiologies of psychiatric illness, but most rely on pathogen mimetics. Here, we developed a mouse model of live H3N2 influenza A virus (IAV) infection during pregnancy that induces a robust inflammatory response but is sublethal to both dams and offspring. We observed classic indicators of lung inflammation and severely diminished weight gain in IAV-infected dams. This was accompanied by immune cell infiltration in the placenta and partial breakdown of placental integrity. However, indications of fetal neuroinflammation were absent. Further hallmarks of mimetic-induced MIA, including enhanced circulating maternal IL-17A, were also absent. Respiratory IAV infection did result in an upregulation in intestinal expression of transcription factor ROR?t, master regulator of a subset of T lymphocytes, T[SUB]H[/SUB]17 cells, which are heavily implicated in MIA-induced etiologies. Nonetheless, subsequent augmentation in IL-17A production and concomitant overt intestinal injury was not evident. Our results suggest that mild or moderately pathogenic IAV infection during pregnancy does not inflame the developing fetal brain, and highlight the importance of live pathogen infection models for the study of MIA.
Keywords: T helper 17 cells; fetal development; fetal neuroinflammation; gestational infection; infection during pregnancy; influenza A virus; influenza infection; maternal immune activation; maternal inflammation; maternal viral infection.