Abstract
In this study we show that murine and human neutrophils are capable of secreting IP-10 in response to communication from the HSV-1 infected cornea and that they do so in a time frame associated with the recruitment of CD8+ T cells and CXCR3-expressing cells. Cellular markers were used to establish that neutrophil influx corresponded in time to peak IP-10 production, and cellular depletion confirmed neutrophils to be a significant source of IP-10 during HSV-1 corneal infection in mice. A novel ex vivo model for human corneal tissue infection with HSV-1 was used to confirm that cells resident in the cornea are also capable of stimulating neutrophils to secrete IP-10. Our results support the hypothesis that neutrophils play a key role in T-cell recruitment and control of viral replication during HSV-1 corneal infection through the production of the T-cell recruiting chemokine IP-10.
Highlights
Herpes simplex virus-type 1 (HSV-1) infection of the human cornea can lead to a damaging inflammatory response known as herpes stromal keratitis (HSK)
We previously used a model for delayed type hypersensitivity (DTH), a secondary immune response to HSV-1 antigen in the skin of mice, to demonstrate that the neutrophil acts as a source for both IP-10 and MIG in the model
We demonstrate the effect of cellular depletion of neutrophils, natural killer cells, and CD4+ T cells on the level of IP-10 production and provide evidence for secretion of IP-10 by neutrophils, in vitro and in vivo, in both murine and human corneal tissue infected by HSV-1
Summary
Herpes simplex virus-type 1 (HSV-1) infection of the human cornea can lead to a damaging inflammatory response known as herpes stromal keratitis (HSK). Mice exhibit an inflammatory response to HSV-1 infection of the cornea which is marked by neutrophil infiltration at days 2 and 9 after infection (p.i.) [6,7,8,9]. Neutrophil depletion studies have demonstrated that in the absence of neutrophils CD8+, T-cell levels are reduced and viral clearance is limited leading to more severe disease development [12, 13]. We previously used a model for delayed type hypersensitivity (DTH), a secondary immune response to HSV-1 antigen in the skin of mice, to demonstrate that the neutrophil acts as a source for both IP-10 and MIG in the model.
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