Susceptibility of human dendritic cells (DCs) to measles virus (MV) depends on their activation stages in conjunction with the level of CDw150: role of Toll stimulators in DC maturation and MV amplification.
Human CD46 (membrane cofactor protein, or MCP) and CDw150 (signaling lymphocyte activation molecule, or SLAM) serve as receptors for measles virus (MV), which induces marked host immune suppression. Although monocytes express CD46, they are considerably resistant to MV. Once monocytes differentiate into immature myeloid dendritic cells (iDCs) (GM-CSF + IL-4-treated), the cells become susceptible to MV. Therefore, we have identified CD46-adapted and CDw150-adapted strains of MV, and the dynamics of CD46 and CDw150 during monocyte-iDC conversion were examined in conjunction with MV susceptibility. Strikingly, CDw150 was not detected in monocytes and moderately induced in iDCs, while CD46 was constantly expressed in monocyte-to-iDC differentiation. Thus, iDCs were found to become highly permissive to CDw150-adapted MV strains via expression of CDw150. In fact, polyclonal and monoclonal antibodies that specifically blocked the MV receptor function of CD46 or CDw150 cancelled MV replication in iDCs according to the preferential usage of either CD46 or CDw150 in each strain of MV. Next, we showed that DCs that matured via stimulation of their Toll-like receptors (TLRs) 2 and/or 4 exhibited an approximately fivefold increase in CDw150 at the protein level, and concomitantly, higher levels of MV amplification were observed in mixed culture of lymphocytes than in iDCs without TLR2/4 stimuli. Hence, amplification of CDw150-dependent MV strains was augmented in DCs parallel with the levels of CDw150 in the presence of lymphocytes possessing CDw150. TLR-mediated functional potential of DCs may affect the degree of MV amplification through distinct MV strain-specific receptor usage of CDw150 or CD46.
Murabayashi
Nozomu
N
Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan.
Kurita-Taniguchi
Mitsue
M
Ayata
Minoru
M
Matsumoto
Misako
M
Ogura
Hisashi
H
Seya
Tsukasa
T
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D029721:Drosophila Proteins; D005434:Flow Cytometry; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008459:Measles virus / Q000235:genetics / Q000254:growth & development* / Q000276:immunology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014709:Vero Cells; D014779:Virus Replication
D015703:Antigens, CD; C497857:CD46 protein, human; D029721:Drosophila Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; D008024:Ligands; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor