ID: 218. Issue 1 (November 2015)

• Record Type: Journal Article
• Authors: Tegtmeyer, Pia-Katharina; Spanier, Julia; Doering, Marius; Hirche, Christoph; Lienenklaus, Stefan; Brizic, Ilija; Jonjic, Stipan; Kalinke, Ulrich
• Is Part Of: Cytokine. Volume 76:Issue 1(2015)
• Page Start: 104
• Page End: 105
• Publication Date: 2015-11
• Subjects: Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.08.222
• Languages: English
• ISSNs: 1043-4666

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p id="sp005">The cytomegalovirus (CMV), a member of the beta-herpesvirus family, is widely spread among the world population and causes lifelong latent infections, which can lead to severe diseases in immunocompromised patients. Therefore, it is important to understand the interplay between different immune mechanisms that are essential for the control of CMV infection.</p> <p id="sp010">To dissect the role of different recognition platforms, MyD88Trif−/− and Cardif−/− mice devoid of TLR- or RLH-dependent signaling, respectively, or MyD88TrifCardif−/− mice and STING−/− mice were i.v. infected with mouse adapted MCMV <inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7m3f" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si1.gif" display="inline" overflow="scroll" id="d13e126" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">Δ</mml:mi></mml:mrow></mml:math></alternatives></inline-formula>m157.</p> <p id="sp015">75% of MyD88TrifCardif−/− mice succumbed to CMV infection within 7 days, whereas basically all MyD88Trif−/−, Cardif−/−, and STING−/− mice survived without signs of severe disease. Nevertheless, analysis of IFN-<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7rqf" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si2.gif" display="inline" overflow="scroll" id="d13e135" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">β</mml:mi></mml:mrow></mml:math></alternatives></inline-formula> reporter mice with the described recognition receptor deficiencies revealed that during the early phase of infection within the liver CMV induced IFN-<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7rqf" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si2.gif" display="inline" overflow="scroll" id="d13e140" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">β</mml:mi></mml:mrow></mml:math></alternatives></inline-formula> in a STING-dependent manner. In contrast, in MyD88TrifCardif−/− IFN-<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7rqf" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si2.gif" display="inline" overflow="scroll" id="d13e145" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">β</mml:mi></mml:mrow></mml:math></alternatives></inline-formula> reporter mice an enhanced reporter induction was detected during early and late phase of infection. In lymph nodes only the second wave of IFN-<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7rqf" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si2.gif" display="inline" overflow="scroll" id="d13e150" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">β</mml:mi></mml:mrow></mml:math></alternatives></inline-formula> production was detectable. This lymph node-specific IFN-<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7rqf" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si2.gif" display="inline" overflow="scroll" id="d13e156" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">β</mml:mi></mml:mrow></mml:math></alternatives></inline-formula> induction was reduced in MyD88TrifCardif−/− mice, whereas its magnitude was comparable in STING−/− and C57BL/6 mice.</p> <p id="sp020">In conclusion, the obtained results indicated an important, but not exclusive role of TLR- and RLH-signaling in protection against MCMV <inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7m3f" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si1.gif" display="inline" overflow="scroll" id="d13e163" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">Δ</mml:mi></mml:mrow></mml:math></alternatives></inline-formula>m157 infection. While STING-dependent signaling was not necessary to protect against CMV infection, it seemed to be crucial for the induction of early IFN-<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7mk5" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si8.gif" display="inline" overflow="scroll" id="d13e168" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>β</mml:mi></mml:mrow></mml:math></alternatives></inline-formula> within the liver.</p> </sec> </abstract>