Authors: Justyna Struzik Lidia SzulcDąbrowska Diana Papiernik Anna Winnicka Marek Niemiałtowski
Publish Date: 2015/07/04
Volume: 160, Issue: 9, Pages: 2301-2314
Abstract
Macrophages are antigenpresenting cells APCs that play a crucial role in the innate immune response and may be involved in both clearance and spread of viruses Stimulation of macrophages via Tolllike receptors TLRs results in activation of nuclear factor κB NFκB and synthesis of proinflammatory cytokines In this work we show modulation of proinflammatory NFκB signaling by a member of the family Poxviridae genus Orthopoxvirus – ectromelia virus ECTV – in RAW 2647 murine macrophages ECTV interfered with p65 NFκB nuclear translocation induced by TLR ligands such as lipopolysaccharide LPS TLR4 polyinosinicpolycytidylic acid polyIC TLR3 and diacylated lipopeptide Pam2CSK4 TLR2/6 We observed that ECTV modulates phosphorylation of Ser32 of inhibitor of κB IκBα and Ser536 of p65 Interference of ECTV with TLR signaling pathways implied that proinflammatory cytokine synthesis was inhibited Our studies provide new insights into the strategies of proinflammatory signaling modulation by orthopoxviruses during their replication cycle in immune cells Understanding important immune interactions between viral pathogens and APCs might contribute to the identification of drug targets and the development of vaccinesWe thank Dr Felix N Toka from WULSSGGW for help with manuscript editing This work was supported by Grant No N N308573740 for MN from the Ministry of Science and Higher Education in Warsaw Grant No 2011/03/B/NZ6/03856 for MN from National Science Center in Cracow and internal research Grant No 505 1002340034 for LSD and No 505 1002340050 for JS from WULSSGGW in Warsaw
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