Journal
MEDICAL MICROBIOLOGY AND IMMUNOLOGY
Volume 208, Issue 6, Pages 703-714Publisher
SPRINGER
DOI: 10.1007/s00430-019-00588-8
Keywords
Zika virus; Patient; Innate immune receptors; Toll-like receptors (TLRs); RIG-like receptors (RLRs); Cytokines
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Funding
- National Council for Scientific and Technological Development (MEC/MCTI/CAPES/CNPq/FAPS-PVE Grant) [400328/2014-3]
- National Council for Scientific and Technological Development (MCTI/CNPq/Universal Grant) [404904/2016-5]
- University Faculty Advanced Studies Coordination Unit (CAPES)
- CNPq
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Innate immunity receptors (Toll-like receptors/TLRs and RIG-like receptors/RLRs) are important for the initial recognition of Zika virus (ZIKV), modulation of protective immune response, and IFN-alpha and IFN-beta production. Immunological mechanisms involved in protection or pathology during ZIKV infection have not yet been determined. In this study, we evaluated the mRNA expression of innate immune receptors (TLR3, TLR7, TLR8, TLR9, melanoma differentiation-associated protein 5/MDA-5, and retinoic acid inducible gene/RIG-1), its adapter molecules (Myeloid Differentiation Primary Response Gene 88/Myd88, Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-beta/TRIF), and cytokines (IL-6, IL-12, TNF-alpha, IFN-alpha, IFN-beta, and IFN-gamma) in the acute phase of patients infected by ZIKV using real-time PCR in peripheral blood. Patients with acute ZIKV infection had high expression of TLR3, IFN-alpha, IFN-beta, and IFN-gamma when compared to healthy controls. In addition, there was a positive correlation between TLR3 expression compared to IFN-alpha and IFN-beta. Moreover, viral load is positively correlated with TLR8, RIG-1, MDA-5, IFN-alpha, and IFN-beta. On the other hand, patients infected by ZIKV showed reduced expression of RIG-1, TLR8, Myd88, and TNF-alpha molecules, which are also involved in antiviral immunity. Similar expressions of TLR7, TLR9, MDA-5, TRIF, IL-6, and IL-12 were observed between the group of patients infected with ZIKV and control subjects. Our results indicate that acute infection (up to 5 days after the onset of symptoms) by ZIKV in patients induces the high mRNA expression of TLR3 correlated to high expression of IFN-gamma, IFN-alpha, and IFN-beta, even though the high viral load is correlated to high expression of TLR8, RIG-1, MDA-5, IFN-alpha, and IFN-beta in ZIKV patients.
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