Lymphoid-related CD11c+ CD8alpha+ dendritic cells are involved in enhancing herpes simplex virus type 1 latency.
The mechanism(s) by which herpes simplex virus type 1 (HSV-1) latency is established in neurons is not known. In this study, we examined the effect of dendritic cells (DCs) on the level of HSV-1 latency in trigeminal ganglia (TGs) of ocularly infected BALB/c and C57BL/6 mice. We found that immunization of wild-type mice with FMS-like tyrosine kinase 3 ligand (Flt3L) DNA, which increases the number of DCs, increased the amount of latency in infected mice. Conversely, depletion of DCs was associated with reduced latency. Latency was also significantly reduced in Flt3L(-/-) and CD8(-/-) mice. Interestingly, immunization of Flt3L(-/-) but not CD8(-/-) mice with Flt3L DNA increased latency. Transfer experiments using DCs expanded ex vivo with Flt3L or granulocyte-macrophage colony-stimulating factor suggested that increased latency was associated with the presence of lymphoid-related (CD11c(+) CD8alpha(+)) DCs, while reduced latency was associated with myeloid-related (CD11c(+) CD8alpha(-)) DCs. Modulation of DC numbers by Flt3L DNA immunization or depletion did not alter acute virus replication in the eye or TG or eye disease in ocularly infected mice. Our results suggest that CD11c(+) CD8alpha(+) DCs directly or indirectly increase the amount of HSV-1 latency in mouse TGs.
Mott
Kevin R
KR
Center for Neurobiology and Vaccine Development, D2024, Cedars-Sinai Burns and Allen Research Institute, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
Underhill
David
D
Wechsler
Steven L
SL
Ghiasi
Homayon
H
D000818:Animals; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015828:Eye Infections, Viral / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology / Q000662:veterinary; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000502:physiology*; D007114:Immunization; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology / Q000276:immunology / Q000821:virology; D017735:Virus Latency / Q000276:immunology*
D039521:CD11c Antigen; D016827:CD8 Antigens; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C084881:flt3 ligand protein; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor