CD8α dendritic cells drive establishment of HSV-1 latency.
It is generally accepted that CD8 T cells play the key role to maintain HSV-1 latency in trigeminal ganglia of ocularly infected mice. Yet, comparably little is known about the role of innate immunity in establishment of viral latency. In the current study, we investigated whether CD8α DCs impact HSV-1 latency by examining latency in the trigeminal ganglia (TG) of wild-type (WT) C57BL/6 versus CD8α-/- (lack functional CD8 T cells and CD8α+ DCs), CD8β-/- (have functional CD8α+ T cells and CD8α+ DCs), and β2m-/- (lack functional CD8 T cells but have CD8α+ DCs) mice as well as BXH2 (have functional CD8 T cells but lack CD8α+ DCs) versus WT C3H (have functional CD8α T cells and CD8α+ DCs) mice. We also determined whether the phenotype of CD8α-/- and BXH2 mice could be restored to that of WT mice by adoptive transfer of WT CD8+ T cells or bone marrow (BM) derived CD8α+ DCs. Our results clearly demonstrate that CD8α DCs, rather than CD8 T cells, are responsible for enhanced viral latency and recurrences.
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns & Allen Research Institute, Los Angeles, California, United States of America.
Kevin R
KR
Mott
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns & Allen Research Institute, Los Angeles, California, United States of America.
Sariah J
SJ
Allen
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns & Allen Research Institute, Los Angeles, California, United States of America.
Mandana
M
Zandian
Departments of Neurosurgery and Biomedical Sciences, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Bindu
B
Konda
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Behrooz G
BG
Sharifi
School of Veterinary Medicine and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, United States of America.
Clinton
C
Jones
Gavin Herbert Eye Institute, The Department of Ophthalmology, The Department of Microbiology and Molecular Genetics, and the Center for Virus Research, University of California Irvine, School of Medicine, Irvine, California, United States of America.
Steven L
SL
Wechsler
Zilkha Neurogenetic Institute, Department of Physiology and Biophysics, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States of America.
Terrence
T
Town
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns & Allen Research Institute, Los Angeles, California, United States of America.
Homayon
H
Ghiasi
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012008:Recurrence; D012668:Trigeminal Ganglion / Q000276:immunology / Q000378:metabolism / Q000821:virology; D017735:Virus Latency / Q000276:immunology*
D016827:CD8 Antigens; C431698:CD8alpha antigen