Natural killer (NK) cells, an important component of innate immunity, are a distinct lineage of lymphocytes defined by the expression of CD56 and NKp46 and by the absence of CD3, providing a first line of defense against pathogens and cancer in a non-major-histocompatibility-complex- (MHC-) restricted fashion without the need of prior sensitization. Derived from the bone marrow, NK cells have wide tissue distribution, with high frequencies of mature ones in lung, liver, blood and spleen.
They are generally found at low frequencies in lymph nodes and mostly with immature phenotype, but following local stimulation, mature NK cells can accumulate in these sites. The function of NK cells is regulated by a balance between signals transmitted by activating receptors, which recognize ligands on tumors and virus-infected cells, and inhibitory receptors specific for MHC-I molecules. NK cells serve as an effective, early protection.
They are activated during the initial stages of viral infections by cytokines and chemokines, such as IFN-𝛼, IFN-𝛽, IL-12, IL-15, and IL-18, produced by infected cells or by interacting with dendritic cells and macrophages. NK cells use two main effector mechanisms to control disease: direct lysis of infected target cells with perforin and granzymes through the granule-exocytosis pathway and the secretion of TNF-𝛼, IFN-𝛾, GM-CSF, and chemokines that are significant in the non-cytolytic control of viral infections and may help shape the subsequent adaptive immune response.
In the battle between host and invading pathogens, virus has also developed several strategies for evading NK cell elimination, including viral-encoded proteins binding to NK cell inhibitory receptor, viral immunoevasion by encoding cytokine mimicry, soluble ligands secreted by virus inhibiting NK cell activity, and directly infecting NK cells. Taking avian influenza for example, NK cells are activated after infection with H9N2 LPAI virus, but not with induction by H5N1 virus, suggesting decreased NK cell activation may be one of the mechanisms contributing to the enhanced pathogenicity of HPAI viruses. Thus, how to reverse the immune suppression of NK cells and boost NK cell activity are crucial for fully usage of NK cells to prevent and treat emerging and severe pathogen infections.
Due to the growing recognition that natural products are non-toxic, have lesser side effects, and are accessible at affordable prices, hub on medicinal plant research has augmented all over the world. Phytocee™, a proprietary polyherbal formulation for poultry and other animal species, is developed by M/s Natural Remedies Private Limited, Bengaluru, India, containing E. officinalis fruits (70% w/w), O. sanctum whole plant (20% w/w), and W. somnifera roots (10% w/w). All these plants are reported for their benefits to immune competence.
PhytoceeTM is already proven to promote lymphocyte proliferation and macrophage activation, and improve antibody titre. The recent research shows that NK cell activity is sensitive to both water and methanol extracts of Phytocee™, exhibiting an increasing trend in a concentration-dependent manner.
This result indicates that Phytocee™ has an ability to control virus expansion before the onset of specific immune response via activation of NK cells, which is a very unique opportunity to support better healthcare for farm animals.