Abstract
Natural killer (NK) cells belong to the innate immune system and play a central role in the defense against viral infections and cancer development, but also contribute to shaping adaptive immune responses. NK cells are particularly important in the first line defense against herpesviruses, including alphaherpesviruses. In addition to their ability to kill target cells and produce interferon-γ, porcine and human NK cell subsets have been reported to display features associated with professional antigen presenting cells (APC), although it is currently unclear whether NK cells may internalize debris of virus-infected cells and whether this APC-like activity of NK cells may stimulate proliferation of antiviral T cells. Here, using the porcine alphaherpesvirus pseudorabies virus (PRV), we show that vaccination of pigs with a live attenuated PRV vaccine strain triggers expression of MHC class II on porcine NK cells, that porcine NK cells can internalize debris from PRV-infected target cells, and that NK cells can stimulate proliferation of CD8+ and CD4+CD8+ PRV-experienced T cells. These results highlight the potential of targeting these NK cell features in future vaccination strategies.
Highlights
Natural killer (NK) cells, members of the innate immune system, play an indispensable role in the defense against viral infections and cancer development, mainly because of their ability to kill virus-infected cells and malignant cells and their ability to produce cytokines, especially interferon-γ (IFNγ)
Using the NK-susceptible cell line K562, we showed that porcine NK cells are able to perform actin polymerizationdependent internalization of cell debris derived from their killed target cells [14]
We investigated whether porcine NK cells may internalize debris from killed pseudorabies virus (PRV)-infected target cells, which is an important prerequisite for potential antigen presenting properties of porcine NK cells in the context of an alphaherpesvirus infection
Summary
Natural killer (NK) cells, members of the innate immune system, play an indispensable role in the defense against viral infections and cancer development, mainly because of their ability to kill virus-infected cells and malignant cells and their ability to produce cytokines, especially interferon-γ (IFNγ). NK cells are important in the first line defense against herpesviruses, including alphaherpesviruses [1]. Patients with NK cell deficiencies have been reported to suffer from aggravated and sometimes life-threatening alphaherpesvirus disease, including herpes simplex virus (HSV) encephalitis [2,3,4,5]. The development of HSV vaccines has proven cumbersome, and has not been successful yet [6, 7]. Designing effective HSV vaccines may require new approaches, targeting previously underestimated elements of the immune response. It has been pointed out that the activity of NK cells may be an underappreciated facet of HSV vaccine design [8]. For pseudorabies virus (PRV), a close relative of HSV in pigs, vaccination using live attenuated vaccines has been very successful [9,10,11]
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