PMID- 27577867
OWN - NLM
STAT- MEDLINE
DCOM- 20171127
LR  - 20181113
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Print)
IS  - 0818-9641 (Linking)
VI  - 95
IP  - 1
DP  - 2017 Jan
TI  - Cornea lymphatics drive the CD8(+) T-cell response to herpes simplex virus-1.
PG  - 87-98
LID - 10.1038/icb.2016.80 [doi]
AB  - Herpes simplex virus-1 (HSV-1) infection of the cornea induces vascular 
      endothelial growth factor A (VEGF-A)-dependent lymphangiogenesis. However, the 
      extent to which HSV-1-induced corneal lymphangiogenesis impacts the adaptive 
      immune response has not been characterized. Here, we used floxed VEGF-A mice to 
      study the importance of newly created corneal lymphatic vessels in the host 
      adaptive immune response to infection. Whereas the mice infected with the 
      parental virus (strain SC16) exhibited robust corneal lymphangiogenesis, mice 
      that received the recombinant virus (SC16 ICP0-Cre) that expresses Cre 
      recombinase under the control of infected cell protein 0 (ICP0), an HSV-1 
      immediate-early gene, showed a significant reduction in lymphangiogenesis. There 
      was no difference in virus recovered from the cornea of mice infected with SC16 
      vs SC16 ICP0-Cre. However, viral loads were significantly elevated in the 
      trigeminal ganglia (TG) of mice with reduced corneal lymphangiogenesis. The 
      increase in viral titer correlated with a significant loss of HSV-1-specific 
      CD8(+) T cells that traffic to the TG of mice infected with the recombinant 
      virus. Intrastromal delivery of size-exclusion dye (fluorescein 
      isothiocyanate-dextran) revealed a time-dependent defect in the ability of the 
      lymphatic vessels in SC16 ICP0-Cre-infected mice to transport soluble antigen 
      from the cornea to the draining lymph nodes. We interpret these results to 
      suggest that the newly created lymphatic vessels in the cornea driven by HSV-1 
      infection are critical in the delivery of soluble viral antigen to the draining 
      lymph node and subsequent development of the CD8(+) T-cell response to HSV-1.
FAU - Gurung, Hem R
AU  - Gurung HR
AD  - Department of Microbiology and Immunology, University of Oklahoma Health Sciences 
      Center, Oklahoma City, OK, USA.
FAU - Carr, Meghan M
AU  - Carr MM
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center, 
      Oklahoma City, OK, USA.
FAU - Carr, Daniel J J
AU  - Carr DJ
AD  - Department of Microbiology and Immunology, University of Oklahoma Health Sciences 
      Center, Oklahoma City, OK, USA.
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center, 
      Oklahoma City, OK, USA.
LA  - eng
GR  - P30 EY021725/EY/NEI NIH HHS/United States
GR  - R01 EY021238/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20160831
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Antigens, Viral)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
CIN - Immunol Cell Biol. 2017 Jan;95(1):5-6. PMID: 28044065
MH  - Animals
MH  - Antigens, Viral/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Cornea/*pathology
MH  - Dendritic Cells/metabolism
MH  - Fibroblasts/pathology
MH  - Herpes Simplex/*immunology/*virology
MH  - Herpesvirus 1, Human/*physiology
MH  - Lymph Nodes/*pathology/*virology
MH  - Lymphangiogenesis
MH  - Mice
MH  - Trigeminal Ganglion/pathology/virology
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - Virus Replication
PMC - PMC5209249
MID - NIHMS808258
COIS- The authors declare no conflict of interest.
EDAT- 2016/09/01 06:00
MHDA- 2017/11/29 06:00
PMCR- 2017/02/28
CRDT- 2016/09/01 06:00
PHST- 2016/06/27 00:00 [received]
PHST- 2016/08/02 00:00 [revised]
PHST- 2016/08/03 00:00 [accepted]
PHST- 2017/02/28 00:00 [pmc-release]
PHST- 2016/09/01 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2016/09/01 06:00 [entrez]
AID - icb201680 [pii]
AID - 10.1038/icb.2016.80 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2017 Jan;95(1):87-98. doi: 10.1038/icb.2016.80. Epub 2016 Aug 
      31.