Estrogen mediates innate and adaptive immune alterations to influenza infection in pregnant mice.
Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.
Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America.
Michael A
MA
Pazos
Thomas A
TA
Kraus
César
C
Muñoz-Fontela
Thomas M
TM
Moran
D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004967:Estrogens / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D011247:Pregnancy; D015398:Signal Transduction
D016207:Cytokines; D004967:Estrogens