Infection of human dendritic cells with herpes simplex virus type 1 dramatically diminishes the mRNA levels of the prostaglandin E(2) receptors EP2 and EP4.
Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) of the immune system. Their migration to secondary lymphoid tissues is a crucial step for the priming of T cells and ultimately for the initiation of adaptive immune responses. Therefore, DCs are potential targets for immune evasion strategies of pathogens. The migration of DCs to the T cell areas of lymph nodes is guided by a gradient of chemokines, CCL19 and CCL21, which are constitutively expressed there. CCR7, the receptor for these chemokines, is expressed on activated DCs, enabling their homing to the lymph nodes. However, CCR7 expression alone is not sufficient for efficient migration. Prostaglandin E(2) (PGE(2)) is a mandatory factor for CCR7-mediated migration of DCs and exerts its effects via prostaglandin E(2) receptor 2 (EP2) and prostaglandin E(2) receptor 4 (EP4). In this study, we investigated the effect of herpes simplex virus type 1 (HSV-1) infection of mature monocyte-derived dendritic cells (MODCs) on the EP2 and EP4 receptor expression. Affymetrix analyses and real-time polymerase chain reaction (PCR) demonstrated a dramatic down-regulation of the expression of those receptors. Additional real-time PCR and migration assays with a Deltavhs mutant virus lacking the virion host shutoff (vhs) gene implicate a vhs independent mechanism. Therefore, our results suggest a novel immune evasion strategy for HSV-1.
Theodoridis
Alexandros A
AA
Department of Dermatology, University Hospital Erlangen, Erlangen, Hartmannstrasse 14, 91052, Erlangen, Germany. alexandros.theodoridis@derma.imed.uni-erlangen.de
Prechtel
Alexander T
AT
Turza
Nadine M
NM
Zenke
Martin
M
Steinkasserer
Alexander
A
D019742:Chemokines, CC / Q000378:metabolism*; D002633:Chemotaxis; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D011458:Prostaglandins E / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype
D019742:Chemokines, CC; C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; D011458:Prostaglandins E; D012333:RNA, Messenger; D054400:Receptors, CCR7; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype