Interferon induced protein 35 exacerbates H5N1 influenza disease through the expression of IL-12p40 homodimer
Publication Date
April 26, 2018
Authors
Anshu P. Gounder, Christine C. Yokoyama, Nicholas N. Jarjour, Traci L. Bricker, et al
Volume
14
Issue
4
Pages
e1007001
DOI
https://dx.plos.org/10.1371/journal.ppat.1007001
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1007001
Scopus
85046484963
Mendeley
http://www.mendeley.com/research/interferon-induced-protein-35-exacerbates-h5n1-influenza-disease-through-expression-il12p40-homodime
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Mendeley | Further Information

{"title"=>"Interferon induced protein 35 exacerbates H5N1 influenza disease through the expression of IL-12p40 homodimer", "type"=>"journal", "authors"=>[{"first_name"=>"Anshu P.", "last_name"=>"Gounder"}, {"first_name"=>"Christine C.", "last_name"=>"Yokoyama"}, {"first_name"=>"Nicholas N.", "last_name"=>"Jarjour"}, {"first_name"=>"Traci L.", "last_name"=>"Bricker"}, {"first_name"=>"Brian T.", "last_name"=>"Edelson"}, {"first_name"=>"Adrianus C. M.", "last_name"=>"Boon"}], "year"=>2018, "source"=>"PLOS Pathogens", "identifiers"=>{"sgr"=>"85046484963", "scopus"=>"2-s2.0-85046484963", "issn"=>"15537374", "pui"=>"622015706", "doi"=>"10.1371/journal.ppat.1007001"}, "id"=>"b390908e-e660-3d98-b8ea-802a87b4a0e4", "abstract"=>"Pro-inflammatory cytokinemia is a hallmark of highly pathogenic H5N1 influenza virus (IAV) disease yet little is known about the role of host proteins in modulating a pathogenic innate immune response. The host Interferon Induced Protein 35 (Ifi35) has been implicated in increased susceptibility to H5N1-IAV infection. Here, we show that Ifi35 deficiency leads to reduced morbidity in mouse models of highly pathogenic H5N1- and pandemic H1N1-IAV infection. Reduced weight loss in Ifi35-/- mice following H5N1-IAV challenge was associated with reduced cellular infiltration and decreased production of specific cytokines and chemokines including IL-12p40. Expression of Ifi35 by the hematopoietic cell compartment in bone-marrow chimeric mice contributed to increased immune cell recruitment and IL-12p40 production. In addition, Ifi35 deficient primary macrophages produce less IL-12p40 following TLR-3, TLR-4, and TLR-7 stimulation in vitro. Decreased levels of IL-12p40 and its homodimer, IL-12p80, were found in bronchoalveolar lavage fluid of H5N1-IAV infected Ifi35 deficient mice. Specific antibody blockade of IL-12p80 ameliorated weight loss and reduced cellular infiltration following H5N1-IAV infection in wild-type mice; suggesting that increased levels of IL-12p80 alters the immune response to promote inflammation and IAV disease. These data establish a role for Ifi35 in modulating cytokine production and exacerbating inflammation during IAV infection.", "link"=>"http://www.mendeley.com/research/interferon-induced-protein-35-exacerbates-h5n1-influenza-disease-through-expression-il12p40-homodime", "reader_count"=>2, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}}, "group_count"=>0}

Scopus | Further Information

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