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10.1371/journal.ppat.1007001

http://scihub22266oqcxt.onion/10.1371/journal.ppat.1007001
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C5940246!5940246!29698474
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suck abstract from ncbi


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pmid29698474      PLoS+Pathog 2018 ; 14 (4): ä
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  • Interferon induced protein 35 exacerbates H5N1 influenza disease through the expression of IL-12p40 homodimer #MMPMID29698474
  • Gounder AP; Yokoyama CC; Jarjour NN; Bricker TL; Edelson BT; Boon ACM
  • PLoS Pathog 2018[Apr]; 14 (4): ä PMID29698474show ga
  • 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.
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