Role for Neutrophils in T Cell Recruitment into the HSV-1 Infected Cornea

Abstract

Abstract: : Purpose: Earlier studies showed that neutrophils were required for efficient suppression of HSV-1 replication in the infected murine cornea. We tested the hypothesis that one antiviral function of neutrophils is to mediate recruitment of immune T cells. Methods: Mice were immunized via HSV-1 infection in footpads plus subcutaneously. Cell depletion was achieved via treatment with mAbs RB6 8C5, GK1.5, and 2.43 which deplete neutrophils, CD4+ T cells, and CD8+ T cells respectively. Virus titers were determined by plaque assay. Messenger RNA levels were assessed via real time RT-PCR. Results: Immunized C57 Bl/6 mice were challenged topically on the cornea with 1x10⁴ PFU HSV-1 (strain RE). Four days after infection animals depleted of neutrophils or CD4+ T cells but not CD8+ T cells had HSV-1 titers in the cornea that were 10²-10³ fold higher than that in non-depleted controls. Purified neutrophils exposed to IL-1α plus IFN-γ increased mRNA levels for the T cell chemoattractants Mig, IP-10, and I-TAC by 3822, 832, and 1351 fold respectively above unstimulated controls. These mRNAs were detected in immune host corneas at 24 and 48 hrs postinfection. The cytokine IL-1α was detected in the same time frame in vivo while IFN-γ was detected only at 48 hrs after infection. Depletion of neutrophils substantially reduced the mRNA level for Mig, but not IP-10 or I-TAC. Conclusions: Collectively, our results suggest that in corneas of immune hosts HSV-1 infection triggers a cascade wherein cytokines act synergistically to induce neutrophils to secret chemokines such as Mig, which can in turn promote virus clearance via recruitment of sensitized CD4+ T cells.

Keywords: cytokines/chemokines • herpes simplex virus • inflammation