Neutrophils Aid in Protection of the Vaginal Mucosae of Immune Mice against Challenge with Herpes Simplex Virus Type 2

Abstract

Large numbers of polymorphonuclear leukocytes (PMNs) infiltrated the murine vaginal mucosa within 24 h after intravaginal inoculation with an attenuated strain of herpes simplex virus type 2 (HSV-2). The role of these cells in resolution of a primary genital infection and in protection of HSV-immune animals against challenge with a fully virulent HSV-2 strain was investigated. Depletion of greater than 95% of the PMNs at the vaginal mucosal surface prior to intravaginal inoculation with an attenuated HSV-2 strain resulted in significantly higher virus titers on days 3 to 7 but only slightly delayed resolution of the primary genital infection. These results suggest that neutrophils helped control the infection but that other immune mechanisms ultimately cleared the virus. Interestingly, depletion of PMNs from HSV-immune mice prior to challenge with a fully virulent HSV-2 strain resulted in a rise in virus titers to levels comparable to those of nonimmune mice and a more pronounced diminution of virus clearance from the vaginal mucosa despite the presence of HSV-specific B and T cells. Levels of gamma interferon (IFN-γ) and HSV-specific antibody were comparable in neutrophil-depleted and control-treated immune mice following HSV-2 challenge, suggesting that RB6-8C5 treatment did not impair T- and B-cell function. Therefore, these results suggest that neutrophils play a role in limiting and clearing HSV-2 vaginal infections and that they are, in association with HSV-specific B and T cells, an important component in immune protection of the vaginal mucosa.

A recombinant multivalent combination vaccine protects againstChlamydiaand genital herpes

“…Significant levels of Th1 responses were induced following immunization, as indicated by the production of high levels of IFN-g compared with IL-4 levels that remained unchanged up to 8 weeks postimmunization. IFN-g has been shown to be involved in the clearance of HSV-2 from the vaginal mucosa of nonimmune mice and in resistance to reinfection in immune mice (Smith, 1994;Milligan & Bernstein, 1997;Milligan et al, 1998). The Groups of mice were immunized as described in Fig.…”

Immunity to vaginal herpes simplex virus‐2 infection in B‐cell knockout mice

“…In support of this interpretation, IFN-c secretion in immune/ challenged mice was abolished by in vivo depletion of T cells with mAb. 7 The IFN-c that was secreted in immune/challenged BALB/c mice up-regulated the expression both of MHC class II antigens in the vaginal epithelium 10 and VCAM-1 in vascular endothelial cells, 17 and it recruited large numbers of T and B lymphocytes to the vaginal mucosa. 10 These responses were blocked by pretreatment in vivo with mAb to IFN-c.…”

“…They concluded that protective immunity in these mice depended mainly on CD4 + lymphocytes. Similarly, Milligan et al 7 concluded that T-cell immunity is required for protection of the vaginal mucosa, even in the presence of high titres of speci®c HSV-2 antibody, and Sin et al 15 reported that a T helper 1 (Th1)-type immune response provided protective immunity against vaginal herpes infection whereas a T helper 2 (Th2)-type immune response worsened the disease.…”

The lack of RNA‐dependent protein kinase enhances susceptibility of mice to genital herpes simplex virus type 2 infection

“…In response to the initial infection, natural killer (NK) cells, NKT cells, and neutrophils are recruited to the area along with the production of a number of soluble factors including interleukin-12 (IL-12), IL-15 and IL-18, all of which are found to contribute to the innate defence against HSV-2. [3][4][5][6] In addition, recognition by toll-like receptor 9 of HSV-2 DNA leads to the production by plasmacytoid dendritic cells of type I interferons (IFNs), 7 a family of antiviral cytokines that have been found to suppress genital HSV-2 replication in vivo. 8 Even though a robust innate immune response ensues, HSV-2 can successfully infect and replicate in the host.…”