Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea

Abstract

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.

Neutrophils in viral infections: Current concepts and caveats

“…The beneficial role of neutrophils has also been confirmed in other viral models. For example, neutrophil depletion resulted in increased viral replication and subsequent mortality in a mouse model of neurotropic mouse hepatitis virus infection [12] and a higher viral load and lethality in a HSV-1 infection of the murine cornea [13], further supporting a key function of neutrophils in antiviral immunity. Data implicating neutrophils in defense against filoviruses that cause hemorrhagic fever have also been reported.…”

Absence of CCR5 increases neutrophil recruitment in severe herpetic encephalitis

“…Neutrophils are the first cells to infiltrate the cornea and they remain the predominant cell type during the development of HSV-1 keratitis [24][25][26]. This neutrophil response is known to both inhibit viral replication and induce corneal lesion [27,28]. In contrast with the present results, Carr and coworkers [22] found decreased neutrophil recruitment into the cornea and trigeminal ganglia in the early stage of HSV-1 infection by corneal route in CCR5 -/mice.…”

Critical Role of IL-17RA in Immunopathology of Influenza Infection

“…However, neutrophils have also been shown to play a role in control and clearance of influenza virus in experimental models (12)(13)(14)(15)(16), and neutrophil depletion resulted in an uncontrolled and ultimately lethal viremia in the reconstructed 1918 influenza model (11). However, neutrophil depletion using the mAb RB6-8C5 is complicated by the concurrent depletion of other monocytes, dendritic cells, and even some CD8 ϩ T cells (17)(18)(19).…”