TY - JOUR
T1 - Pandemic H1N1 influenza A viruses suppress immunogenic RIPK3-driven dendritic cell death
AU - Hartmann, Boris M.
AU - Albrecht, Randy A.
AU - Zaslavsky, Elena
AU - Nudelman, German
AU - Pincas, Hanna
AU - Marjanovic, Nada
AU - Schotsaert, Michael
AU - Martínez-Romero, Carles
AU - Fenutria, Rafael
AU - Ingram, Justin P.
AU - Ramos, Irene
AU - Fernandez-Sesma, Ana
AU - Balachandran, Siddharth
AU - Garciá-Sastre, Adolfo
AU - Sealfon, Stuart C.
N1 - Funding Information:
This work was supported by PRIME (Program for Research on Immune Modeling and Experimentation), an NIAID-funded Modeling Immunity for Biodefense Center (Grant U19 AI117873), and was partly supported by CRIP (Center for Research on Influenza Pathogenesis), an NIAID-funded Center of Excellence in Influenza Research and Surveillance (CEIRS, contract number HHSN272201400008C), and U19 AI106754. We thank Yongchao Ge for his advice on statistical analysis, Richard Cadagan for technical assistance, and Florian Krammer for providing soluble HA. We are thankful to Kirsten St. George at Kirsten St. George Wadsworth Center for providing the NY/12 and NY/14 IAV strains.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - The risk of emerging pandemic influenza A viruses (IAVs) that approach the devastating 1918 strain motivates finding strain-specific host-pathogen mechanisms. During infection, dendritic cells (DC) mature into antigen-presenting cells that activate T cells, linking innate to adaptive immunity. DC infection with seasonal IAVs, but not with the 1918 and 2009 pandemic strains, induces global RNA degradation. Here, we show that DC infection with seasonal IAV causes immunogenic RIPK3-mediated cell death. Pandemic IAV suppresses this immunogenic DC cell death. Only DC infected with seasonal IAV, but not with pandemic IAV, enhance maturation of uninfected DC and T cell proliferation. In vivo, circulating T cell levels are reduced after pandemic, but not seasonal, IAV infection. Using recombinant viruses, we identify the HA genomic segment as the mediator of cell death inhibition. These results show how pandemic influenza viruses subvert the immune response.
AB - The risk of emerging pandemic influenza A viruses (IAVs) that approach the devastating 1918 strain motivates finding strain-specific host-pathogen mechanisms. During infection, dendritic cells (DC) mature into antigen-presenting cells that activate T cells, linking innate to adaptive immunity. DC infection with seasonal IAVs, but not with the 1918 and 2009 pandemic strains, induces global RNA degradation. Here, we show that DC infection with seasonal IAV causes immunogenic RIPK3-mediated cell death. Pandemic IAV suppresses this immunogenic DC cell death. Only DC infected with seasonal IAV, but not with pandemic IAV, enhance maturation of uninfected DC and T cell proliferation. In vivo, circulating T cell levels are reduced after pandemic, but not seasonal, IAV infection. Using recombinant viruses, we identify the HA genomic segment as the mediator of cell death inhibition. These results show how pandemic influenza viruses subvert the immune response.
UR - http://www.scopus.com/inward/record.url?scp=85037151051&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-02035-9
DO - 10.1038/s41467-017-02035-9
M3 - Article
C2 - 29203926
AN - SCOPUS:85037151051
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1931
ER -