Natural killer cells in host defense against veterinary pathogens

Abstract

Natural Killer (NK) cells constitute a major subset of innate lymphoid cells that do not express the T- and B-cell receptors and play an important role in antimicrobial defense. NK cells not only induce early and rapid innate immune responses, but also communicate with dendritic cells to shape the adaptive immunity, thus bridging innate and adaptive immunity. Although the functional biology of NK cells is well-documented in a variety of infections in humans and mice, their role in protecting domestic animals from infectious agents is only beginning to be understood. In this article, we summarize the current state of knowledge about the contribution of NK cells in pathogen defense in domestic animals, especially cattle and pigs. Understanding the immunobiology of NK cells will translate into strategies to manipulate these cells for preventive and therapeutic purposes.

Keywords: Domestic animals; Immunity; Innate lymphoid cells; NK cells; Pathogens.

Fig. 1

Mechanisms of NK-cell responses. (A) Missing self-model. NK cells possess KIRs that recognize MHC-I molecules on uninfected cells, whereas cells that do not express MHC-I molecules such as infected cells (ICs) are eliminated by NK cells via perforin and granzyme pathway. (B) IFN-γ-mediated direct killing of infected cell. Activation of NK cells results in production of IFN-γ which in turn induces nitric oxide (NO) secretion that causes lysis of the cell. (C) Antibody-dependent cellular cytotoxicity (ADCC). Fc receptors present on NK cells have the ability to bind to fab region of an antibody molecule, whilst variable region of the antibody specifically binds to the surface antigen expressed from pathogens inside the infected cell. Cross-linking of Fc receptors triggers apoptosis of the ICs via perforin and granzyme. (D) DC-NK interaction. Induction of adaptive immune response by modulating DC function. Cytokine production by activated NK cells (IFN-γ/TNF-α) causes DC maturation. Mature DCs polarize T cells via cytokines like IL-12 and IL-23. Polarized T cells induce killing of infected cells through IFN-γ/IL-17, and perforin and granzyme pathway. DC can also activate NK cells through IFN-α/β, and IL-12/18/15.