Lymphocytic choriomeningitis virus infection of dendritic cells interferes with TLR-induced IL-12/IL-23 cytokine production in an IL-10 independent manner. (August 2018)

• Record Type: Journal Article
• Authors: Che Mat, Nor Fazila; Siddiqui, Sarah; Mehta, Divya; Seaver, Kyle; Banete, Andra; Alothaimeen, Torki; Gee, Katrina; Basta, Sameh
• Is Part Of: Cytokine. Volume 108(2018)
• Page Start: 105
• Page End: 114
• Publication Date: 2018-08
• Subjects: TLR -- Cytokines -- BMDC -- Virus; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2018.03.017
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: The IL-12 family of cytokines are important in supporting T cell immune responses. We demonstrate that TLR activation was negatively affected by viral infection. We monitored proteins affected by the infection that regulate cytokine expression. Abstract: Dendritic cells produce IL-12 and IL-23 in response to viral and bacterial infection and these cytokines are responsible for successful pathogen clearance. How sequential viral and bacterial infections affect the production of IL-12 and IL-23 is currently not known. Our study demonstrates that in dendritic cells infected with Lymphocytic choriomeningitis virus (LCMV), TLR activation with bacterial PAMPs resulted in reduced IL-12 and IL-23 expression compared to non-infected cells. Furthermore, expression of other proinflammatory cytokines, TNF-α and IL-6, were not inhibited under these conditions. We discovered that TLR-induced phosphorylation of p38 was significantly inhibited in LCMV-infected cells. We detected enhanced expression of suppressor of cytokine signalling (SOCS)-3 and IL-10. Yet, neutralizing IL-10 did not restore IL-12/IL-23 expression. Taken together, these results show that virus infection interferes with the magnitude of TLR-mediated inflammatory responses by repressing specific cytokine expression.