An increase in herpes simplex virus type 1 in the anterior segment of the eye is linked to a deficiency in NK cell infiltration in mice deficient in CXCR3.
In response to ocular herpes simplex virus type 1 (HSV-1) infection in mice, a rapid induction or increase in the local expression of chemokines, including CXCL10, is found. The present study investigated the role of the receptor for CXCL10, CXCR3, in the host response to corneal HSV-1 infection. Mice deficient in CXCR3 (CXCR3(-/-)) were found to have an increase in infectious virus in the anterior segment of the eye by day 7 postinfection. Coinciding with the increase, selective chemokines, including CCL2, CCL3, CCL5, CXCL9, and CXCL10, were elevated in the anterior segment of the HSV-1-infected CXCR3(-/-) mice. In contrast, there was a time-dependent reduction in the recruitment of natural killer (NK) cells (NK1.1(+)CD3(-)) into the anterior segment of CXCR3(-/-) mice. A reduction in NK cells residing in the anterior segment of mice following antiasialoGM1 antibody treatment resulted in an increase in infectious virus. No other leukocyte populations infiltrating the tissue were modified in the absence of CXCR3. Collectively, the loss of CXCR3 expression specifically reduces NK cell mobilization into the cornea in response to HSV-1.
Carr
Daniel J J
DJ
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. dan-carr@ouhsc.edu
Wuest
Todd
T
Ash
John
J
D000818:Animals; D000869:Anterior Eye Segment / Q000473:pathology* / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D003316:Corneal Diseases / Q000473:pathology / Q000821:virology; D005260:Female; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D007694:Killer Cells, Natural / Q000166:cytology*; D008297:Male; D051379:Mice; D054367:Receptors, CXCR3 / Q000172:deficiency*; D013997:Time Factors; D014779:Virus Replication
D018925:Chemokines; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3