Studies done by Duangkhae 2018 showed that DENV likely mediates LC migration to the dermis where these cells further get infected [11]. immune system that support DENV infection and their corresponding receptors that DENV deploy to gain access to the cells. includes enveloped viruses (approximately 50 nm in diameter) containing a positive sense, single-stranded RNA (approximately 11 kb in size) genome. Dengue virus (DENV) is one such arbovirus having a genome encoding three structural proteins (C, prM/M, E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) [1]. The envelope of the mature virus contains 180 copies of two glycoproteins, e and prM [2]. Depending on the heterogeneity in these two surface proteins, DENV is broadly classified into four serotypes and each serotype is further distinguished into different genotypes [3]. DENV, being an arbovirus, entirely depends on its insect vectors and for circulation in the environment and ultimately reaches its human host for extensive proliferation. Once DENV gains access to the host, it infects different organs and replicates in multiple cells. DENV exploits various cellular receptors to enter the cells. Although various cellular receptors have been identified as receptors for virus entry, non-e of them have been recognized as a universal receptor for DENV entry. Here, we will discuss the immune cells that are known to harbor DENV during the disease progression and the corresponding receptors studied so far. It remains an underexplored field and we are yet to nail down the primary receptor/s involved in the entry process. A better understanding of the receptor usage might help designing specific antiviral candidate/s against DENV infection further. 2. DENV Entry Receptors in Cells of the Immune System 2.1. Dendritic Cells (DCs) Broadly, there are two subsets of DCs found in the mammalian system: Interferon (IFN) secreting, blood and lymphoid tissue-resident plasmacytoid DC (pDC) and antigen-presenting, lymphoid and non-lymphoid tissue-resident myeloid or conventional dendritic cells (mDCs or cDCs). The antigen-presenting property of DC has been exploited by DENV to disseminate from the skin to various lymphoid organs. Also, a common monocyte-DC precursor Asenapine maleate differentiates to give rise to tissue-resident macrophages and monocyte-derived DCs (moDC) which are nonconventional DCs [1]. The immature DCs (iDCs) particularly in the skin Langerhans cells (LCs), dermal cDC and moDC} and in blood have been shown to be more susceptible to DENV infection than mature DC, and DENV infects these cells independent of Fc receptor [4,5,6]. pDCs are not found to be DENV targets Rabbit Polyclonal to Catenin-gamma as significantly lower levels of DENV replication was observed when compared to moDC [7,8]. Previous experiments proved LCs in the epidermis to be the primary targets of DENV in the skin, however, subsequent experiments suggested that DENV is probably released in the dermal layer of the skin affecting its resident cells first [4,9,10]. Hence, the route by which epidermal-resident cells (LC and keratinocytes) Asenapine maleate get infected is still unclear. Studies done by Duangkhae 2018 showed that DENV likely mediates LC migration to the dermis where these cells further get infected [11]. Asenapine maleate Also, studies done by other groups indicate dermal cDCs and macrophages to play a more significant role than LCs in DENV spread [10,12]. The most extensively studied DC receptors are DC-SIGN(CD209) [4,13,14,15], Mannose receptor (MR) [16,17], Langerins [18,19] and Fc receptors [7,20,21]. Other potential receptors expressed in DC include TIM3, TIM4 [22,23,24] and AXL [25]. DC-SIGN, a C type lectin pathogen recognition receptor, is highly expressed in immature DCs like resident dermal DCs (CD14+), monocyte-derived DC in the dermis, DC in the lymph node, {thymus and lungs,|lungs and thymus,} {myeloid DCs in blood and also in dermal and alveolar macrophages [7,|myeloid DCs in blood and in dermal and alveolar macrophages [7 also,}8,10,13,15,26,27]. Although, in presence of Ca2+.