Monocyte Recruitment to the Dermis and Differentiation to Dendritic Cells Increases the Targets for Dengue Virus Replication

Michael A. Schmid*, Eva Harris*

PLoS Pahtog 2014 Dec 4: 10(12): e1004541.

Speaker: Ko-Lun, Yen (顏克倫)              Time: 15:00~16:00, Jun, 03, 2015

Commentator: Yee-Shin, Lin (林以行 教授)   Place: Room 601

Abstract:

Dengue is a tropical infectious disease which is spread by the mosquito Aedes species. There has been a worldwide increase in geographic expansion, and the World Health Organization (WHO) considers half the world at risk for infection. There are currently no specific vaccine or therapeutics exists against dengue. The 4 virus serotype (DENV1-4) dengue causes the most common prevalent arhtropod-borne viral disease in humans. The skin is the barrier to the environment and provides a first line of defense against invasion of microbial pathogens^[1]. Dendritic cells (DCs) and marcophages serve as immune sentinels in the skin, where several subsets of DCs have been identified in the steady-state skin, such as the containing epidermis Langerhan cells (LCs) and the CD103⁺ classical DCs (cDCs) and CD11b⁺ DCs in the dermis. Although previous studies have examined DENV infection in the epidermis; however, there are no information about DENV infection and the immune response in the dermis, where DENV is likely infected. Here, the authors used mice lacking the interferon-a/b receptor (Ifnar^-/-), which allow them to be susceptible to intradermal DENV infection^[2], to investigate the dynamics of immune cells in the skin during early DENV infection. The authors demonstrated recruitment, which is likely mediated by dermis homing factor CCR2^[3], of adoptively-transferred Ly6C^high monocytes from origin to the DENV-infected dermis and subsequent differentiation into Ly6C⁺ CD11b⁺ monocyte-derived DCs (moDCs), which were the major targets for virus replication after 48 hours DENV infection in the dermis. The result revealed the dermis as the main site of early DENV infection and highlights the skin as a potential site for therapeutic action or intradermal vaccination.

Reference:

1.     Pasparakis M, Haase I, Nestle FO (2014) Mechanism regulating skin immunity and inflammation. Nat Rev Immunol 14: 289-301.

2.     Orozco S, Schmid MA, Parameswaran P, Lachica R, Henn MR, et al. (2012) Characterization of a model of lethal dengue virus 2 infection in C57BL/6 mice deficient in the alpha/beta interferon receptor. J Gen Virol 93: 2152-2157.

3.     Serbina NV, Pamer EG (2006) Monocyte emigration from bone marrow during bacterial infection requires signal mediated by chemokine receptor CCR2. Nat Immunol 7: 311-317.