Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea.
Herpes simplex virus type 1 (HSV-1) infection of the murine cornea induces the rapid infiltration of neutrophils. We investigated whether these cells could influence virus replication. BALB/c mice treated with monoclonal antibody (MAb) RB6-8C5 experienced a profound depletion of neutrophils in the bloodstream, spleen, and cornea. In these animals, virus titers in the eye were significantly higher than those in the immunoglobulin G-treated controls at 3 days postinfection. By day 9, virus was no longer detectable in the controls, whereas titers of 10(3) to 10(6) PFU were still present in the neutrophil-depleted hosts. Furthermore, virus spread more readily to the skin and brains of MAb RB6-8C5-treated animals, rendering them significantly more susceptible to HSV-1-induced blepharitis and encephalitis. Only 25% of the treated animals survived, whereas all of the controls lived. Although MAb RB6-8C5 treatment did not alter the CD4+ T-cell, B-cell, natural killer cell, or macrophage populations, the CD8+ T-cell population was partially reduced. Therefore, the experiments were repeated in severe combined immunodeficiency mice, which lack CD8+ T cells. Again virus growth was found to be significantly elevated in the eyes, trigeminal ganglia, and brains of the MAb RB6-8C5-treated hosts. These results strongly indicate that in both immunocompetent and immunodeficient mice, neutrophils play a significant role in helping to control the replication and spread of HSV-1 after corneal infection.
Tumpey
T M
TM
Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile 36688, USA.
Chen
S H
SH
Oakes
J E
JE
Lausch
R N
RN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001762:Blepharitis / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002522:Chlorocebus aethiops; D005123:Eye / Q000821:virology; D005260:Female; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000821:virology; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009504:Neutrophils / Q000276:immunology*; D014709:Vero Cells; D014779:Virus Replication
D000911:Antibodies, Monoclonal