PMID- 32516406
OWN - NLM
STAT- MEDLINE
DCOM- 20210101
LR  - 20211231
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 61
IP  - 6
DP  - 2020 Jun 3
TI  - Role of TH17 Responses in Increasing Herpetic Keratitis in the Eyes of Mice 
      Infected with HSV-1.
PG  - 20
LID - 10.1167/iovs.61.6.20 [doi]
LID - 20
AB  - PURPOSE: TH17 cells play an important role in host defense and autoimmunity yet 
      very little is known about the role of IL17 in herpes simplex virus (HSV)-1 
      infectivity. To better understand the relationship between IL17 and HSV-1 
      infection, we assessed the relative impact of IL17A-deficiency and deficiency of 
      its receptors on HSV-1 responses in vivo. METHODS: We generated IL17RA-/- and 
      IL17RA-/-RC-/- mice in-house and infected them along with IL17A-/- and IL17RC-/- 
      mice in the eyes with 2 x 105 PFU/eye of wild type (WT) HSV-1 strain McKrae. WT 
      C57BL/6 mice were used as control. Virus replication in the eye, survival, 
      corneal scarring (CS), angiogenesis, levels of latency-reactivation, and levels 
      of CD8 and exhaustion markers (PD1, TIM3, LAG3, CTLA4, CD244, and CD39) in the 
      trigeminal ganglia (TG) of infected mice were determined on day 28 postinfection. 
      RESULTS: No significant differences in virus replication in the eye, survival, 
      latency, reactivation, and exhaustion markers were detected among IL17A-/-, 
      IL17RA-/-, IL17RC-/-, IL17RA-/-RC-/-, and WT mice. However, mice lacking IL17 had 
      significantly less CS and angiogenesis than WT mice. In addition, angiogenesis 
      levels in the absence of IL17RC and irrespective of the absence of IL17RA were 
      significantly less than in IL17A- or IL17RA-deficient mice. CONCLUSIONS: Our 
      results suggest that the absence of IL17 protects against HSV-1-induced eye 
      disease, but has no role in protecting against virus replication, latency, or 
      reactivation. In addition, our data provide rationale for blocking IL17RC 
      function rather than IL17A or IL17RA function as a key driver of HSV-1-induced 
      eye disease.
FAU - Hirose, Satoshi
AU  - Hirose S
AD  - ,.
FAU - Jaggi, Ujjaldeep
AU  - Jaggi U
AD  - ,.
FAU - Wang, Shaohui
AU  - Wang S
AD  - ,.
FAU - Tormanen, Kati
AU  - Tormanen K
AD  - ,.
FAU - Nagaoka, Yoshiko
AU  - Nagaoka Y
AD  - ,.
FAU - Katsumata, Makoto
AU  - Katsumata M
AD  - ,.
FAU - Ghiasi, Homayon
AU  - Ghiasi H
AD  - ,.
LA  - eng
GR  - R01 EY015557/EY/NEI NIH HHS/United States
GR  - R01 EY029677/EY/NEI NIH HHS/United States
GR  - R01 EY024649/EY/NEI NIH HHS/United States
GR  - R01 EY014966/EY/NEI NIH HHS/United States
GR  - R01 EY026944/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Biomarkers)
RN  - 0 (Il17a protein, mouse)
RN  - 0 (Interleukin-17)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Corneal Neovascularization/metabolism/physiopathology/virology
MH  - Disease Models, Animal
MH  - Herpesvirus 1, Human/*physiology
MH  - Interleukin-17/metabolism
MH  - Keratitis, Herpetic/metabolism/*physiopathology/virology
MH  - Latent Infection
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polymerase Chain Reaction
MH  - Th17 Cells/*physiology
MH  - Virulence
MH  - Virus Latency/physiology
MH  - Virus Replication/physiology
PMC - PMC7415293
COIS- Disclosure: S. Hirose, None; U. Jaggi, None; S. Wang, None; K. Tormanen, None; Y. 
      Nagaoka, None; M. Katsumata, None; H. Ghiasi, None
EDAT- 2020/06/10 06:00
MHDA- 2021/01/02 06:00
PMCR- 2020/06/09
CRDT- 2020/06/10 06:00
PHST- 2020/06/10 06:00 [entrez]
PHST- 2020/06/10 06:00 [pubmed]
PHST- 2021/01/02 06:00 [medline]
PHST- 2020/06/09 00:00 [pmc-release]
AID - 2766326 [pii]
AID - IOVS-20-30081 [pii]
AID - 10.1167/iovs.61.6.20 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2020 Jun 3;61(6):20. doi: 10.1167/iovs.61.6.20.