Viral replication in placental MCs recommend a role of the cell in vertical transmission (217). Then, many questions stay to become resolve in regards to the function of MCs in defense against Zika virus. With regards to receptors involved in MCs response to viruses, the cytosolic receptors take part in the increased expression of TNF-a and IL-1b, as well as type I IFNs, such as IFN-b and Mx2, as shown by BMMCs infected with all the vesicular stomatitis virus (VSV) (118). It can be critical to mention that kind I IFNs play important roles in innate host defense against viral infections (218), since right after VEGFR-3 Proteins Biological Activity binding to their receptors they activate the expression of numerous genes that promote an “antiviral state”Frontiers in Immunology www.frontiersin.orgJune 2021 Volume 12 ArticleJimenez et al.MC CX3CR1 Proteins Formulation responses to PathogensFIGURE 5 MC-released mediators and signaling pathways in response to viruses. Some viral particles are recognized directly by membrane receptors, i.e. vaccinia virus binds sphingosine-1-phosphate two (S1P2) receptor and human immunodeficiency virus (HIV) to CXCR4, triggering signaling pathways leading to cathelicidin or CXCL8 and CCL3 chemokines release, respectively. Intracellular dengue virus (DENV) is in all probability recognized by RIG-1 and MDA5 and herpes simplex virus (HSV) straight or through the release of alarmin IL-33 by other cells result in the secretion of cytokines and chemokines, with each other with the arachidonic acid derivatives prostaglandin two (PGD2) and 12-hydroxyeicosatetranoic acid (12-HETES). Fv endogen superantigen from hepatocytes infected by hepatitis viruses (HVs) promotes MC degranulation and the release of leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) by a mechanism that appears to rely on the activation of FcRI receptor and calcium mobilization. Zika virus infection promotes MC degranulation and cytokine secretion. Lastly, classical responses to viral compounds by means of TLR3, TLR7 and TLR9 receptors have been observed in MCs, that lead to the synthesis of interferon (IFN)-a and IFN-b via the activation of interferon regulatory factor (IRF)-7 and NFkB, as well as to the release of tryptase and chymase. Solid-lines indicate recognized pathways and dashed-lines show reported effects of receptor triggering or MC-virus interactions, though certain signaling cascades stay to be described.in cells (219). Transcripts for MDA5 and retinoic acid-inducible gene-1 were discovered up-regulated right after the infection of MCs with DENV (212, 220) and with VSV, top to the synthesis of IL-6, IFN-b and IFN-a during VSV infection (221). The activation on the cell by viruses was also dependent around the TLR pathways (222). Activation of TLR3, TLR7 and TLR9 by their respective ligands, polyI:C (double-stranded (ds)RNA analog, TLR3 agonist), R:848 (synthetic TLR7 agonist), and CpG oligodeoxynucleotide (unmethylated consensus DNA sequences, TLR9 agonist), respectively, did not trigger degranulation, but induced the production of TNF-a, IL-6, CCL5/RANTES, CCL3/MIP-1a and CXCL2/MIP-2 by murine fetal skin-derived MCs but not by murine BMMCs (223). In addition to, a current study showed that the stimulation of cultured human peripheral blood-derived MCs (PBMCs) with polyI:C or R848 induced MC activation plus the release of chymase,tryptase, IL-8, CCL3/MIP-1a and CCL4/MIP-1b (224), highlighting the diverse functionality of MCs according to their location and origin. In this context, cultured human PBMCs produced IFN-a through TLR3 in response to RSV, reovirus kind 1 and polyI.