Lactoferrin-mediated protection of the host from murine cytomegalovirus infection by a T-cell-dependent augmentation of natural killer cell activity

Abstract

The administration of bovine lactoferrin (LF) with 1 mg/g body weight before the murine cytomegalovirus (MCMV) infection completely protected the BALB/c mice from death due to the infection. In these LF-treated mice, a significant increase in the activity was found in the NK cells but not in the cytolytic T lymphocytes which recognized an MCMV-derived peptide. Moreover, the elimination of the NK cell activity by an injection with anti-asialo GM1 antibody abrogated such augmented resistance, thus supporting the hypothesis that the LF-mediated antiviral effect in vivo is performed through the augmentation of NK cell activity. No such LF-mediated antiviral effect in vivo with the increased NK cell activity was found in athymic nude mice, whereas it was restored completely by the transfer of splenic T cells from LF-treated donors. These findings therefore suggest that T lymphocytes induce both the augmentation of NK cell activity and the resultant antiviral effect in the LF-treated hosts.

Role of Nitric Oxide Synthase Type 2 in Acute Infection with Murine Cytomegalovirus

“…The NK cell cytotoxicity was determined as described previously (15). In brief, spleen cells were prepared from both NOS2 Ϫ/Ϫ and NOS2 ϩ/ϩ mice infected with 2 ϫ 10 4 PFU MCMV on day 0.…”

“…Among them, Th1-associated cytokine IFN-␥ produced by NK cells or T cells have been shown to play an important role in the clearance of MCMV (12)(13)(14). Moreover, this factor also plays an important role in augmenting the early NK cell response (15) and late protective T cell response (16) to MCMV infection.…”

Milk Derived Peptides with Immune Stimulating Antiviral Properties

“…Binding to hemagglutinin of virus [36,53,135] modified human serum [94,[101][102][103] [12][13][14][15][16] chemically modified milk proteins like serum albumin, -lactalbumin, -lactoglobulin…”

“…interleukin-1,-6,-8,-18, interferon-and tumor necrosis factor- [132]. The antiviral effect of lactoferrin on cytomegalovirus in a murine infection model has been demonstrated to be a result of augmentation of natural killer cell activity rather than of the cytolytic T-lymphocytes [14]. Similarly, human lactoferrin has also been proven to have an effect on natural killer cell cytotoxicity against haematopoietic and epithelial tumor cells [133].…”

“…lactoferricin) have been studied extensively for its antiviral properties [8][9][10] i.e. its direct interaction with the virus particle, interaction with cellular receptors on the target cells, and lately more complex antiviral mechanisms involving stimulation and regulation of the immune system have been discovered [2,[11][12][13][14][15][16]. Similarly, peptides tailored on specific protein fragments of casein and -lactalbumin have also been investigated for their antiviral and immunomodulatory properties.…”