γδ T17 Cells Regulate the Acute Antiviral Response of NK Cells in HSV-1-Infected Corneas

被引:0
|
作者
Rodenberg, Rachel R. [1 ]
Spadafora, Domenico [2 ]
Fitzpatrick, Steffani [1 ,4 ]
Daly, Grant [3 ]
Lausch, Robert [1 ]
Barrington, Robert A. [1 ,2 ]
机构
[1] Univ S Alabama, Dept Microbiol & Immunol, MSB 2114,5851 USA Dr North, Mobile, AL 36604 USA
[2] Univ S Alabama, Flow Cytometry Shared Resources Lab, Mobile, AL 36604 USA
[3] Univ S Alabama, Dept Pharmacol, Mobile, AL 36604 USA
[4] Ceva Anim Hlth, Lenexa, KS USA
关键词
gamma S T cells; interleukin; 17A; natural killer cells; interferon gamma; granzyme; herpes simplex virus 1; corneal opacity; NATURAL-KILLER-CELLS; SIMPLEX-VIRUS TYPE-1; T-CELLS; HOST-DEFENSE; IFN-GAMMA; INFECTION; IL-17A; MICE; RECRUITMENT; INTERLEUKIN-17;
D O I
10.1167/iovs.65.13.16
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
P URPOSE . To determine whether gamma S T cells regulate natural killer (NK) cells in the herpes simplex virus 1 (HSV-1)-infected cornea. M ETHODS . CD57Bl/6 (wild-type [WT]), TCRS-/-, and IFN-gamma-/- mice were infected intracorneally with HSV-1. TCR-/- mice were treated with IL-17A at 24 hours post-infection (PI), and the WT mice received treatments of fingolimod (FTY720) and anti-IL-17A. At 48 hours PI, corneas were excised, and intracellular staining flow cytometry was performed, as well as multiplex analysis. Additionally, single-cell RNA sequencing (scRNAseq) was done to analyze the transcriptome of NK cells from WT and TCRS-/- mice. R ESULTS . In mice lacking gamma S T cells, there were significantly fewer NK cells following ocular HSV-1 infection. This reduction of NK cells corresponded with lower levels of cytokines and chemokines associated with the antiviral response. Furthermore, NK cells from WT mice had enriched IL-17A signaling compared to those from TCRS-/- mice. The NK cell response was partially rescued in TCRS-/- mice by administration of IL-17A. Correspondingly, the NK cell response could be blunted in WT mice by administration of anti-IL-17A. Finally, IFN-gamma-/- mice had significantly less IL-17A production compared to WT mice. C ONCLUSIONS . gamma S T17 cells promote NK cell accumulation in HSV-1-infected corneas. In turn, NK cells secrete IFN-gamma, which negatively regulates further IL-17A production by gamma S T cells.
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页数:11
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