|RAJAO, DANIELA - Non ARS Employee|
|WAIDE, EMILY - Iowa State University|
|GAUGER, PHILLIP - Iowa State University|
|DEKKERS, JACK - Iowa State University|
|TUGGLE, CHRISTOPHER - Iowa State University|
Submitted to: Journal of Innate Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/24/2016
Publication Date: 3/1/2017
Citation: Rajao, D.S., Loving, C.L., Waide, E.H., Gauger, P.C., Dekkers, J.C., Tuggle, C.K., Vincent, A.L. 2017. Pigs with severe combined immunodeficiency are impaired in controlling influenza virus infection. Journal of Innate Immunity. 9(2):193-202.
Interpretive Summary: Pigs are natural hosts for Influenza A viruses (IAV) and an excellent model for human IAV. A severe combined immunodeficiency (SCID) genetic defect was recently detected in pigs, resulting in a drastic impairment in SCID pig's ability to fight infections. These SCID pigs were characterized to have an absence of functional adaptive immune cells (B and T lymphocytes), but maintained the presence of innate immune cells. In this study, the SCID pigs were used to test the ability of the innate immune response to clear IAV infection. SCID pigs showed milder lung pathology, but higher viral titers in lungs and nasal swabs compared to controls, indicating that innate immunity was insufficient for controlling IAV in pigs. These SCID pigs provide a valuable model to understand the immune mechanisms associated with protection and recovery in a natural host for influenza.
Technical Abstract: Influenza A viruses (IAV) infect many host species, including humans and pigs. Severe Combined Immunodeficiency (SCID) is a condition characterized by a lack of T, B, and/or natural killer (NK) cells. Animal models of SCID have great value for biomedical research. Here, we evaluated the pathogenesis and the innate immune response to 2009 H1N1 pandemic IAV (H1N1pdm09) using a recently identified line of naturally occurring SCID pigs that lack T and B lymphocytes, but still have functional NK cells. SCID pigs challenged with H1N1pdm09 showed milder lung pathology compared to the non-SCID heterozygous carrier pigs. Viral titers in the lungs and nasal swabs of challenged SCID pigs were significantly higher than in carrier pigs 7 days post infection (dpi), despite higher levels of IL-1beta and IFN-alpha in the lungs of SCID pigs. The lower levels of inflammatory pathology could be ascribed to the lack of T and B cells responding to the infection, indicating that innate immunity is insufficient for controlling IAV in pigs. This recently identified line of SCID pigs provides a valuable model to understand the immune mechanisms associated with influenza protection and recovery in a natural host for IAV.