Regulation of the human NK cell compartment by pathogens and vaccines

Abstract

Natural killer cells constitute a phenotypically diverse population of innate lymphoid cells with a broad functional spectrum. Classically defined as cytotoxic lymphocytes with the capacity to eliminate cells lacking self-MHC or expressing markers of stress or neoplastic transformation, critical roles for NK cells in immunity to infection in the regulation of immune responses and as vaccineinduced effector cells have also emerged. A crucial feature of NK cell biology is their capacity to integrate signals from pathogen-, tumor-or stress-induced innate pathways and from antigenspecific immune responses. The extent to which innate and acquired immune mediators influence NK cell effector function is influenced by the maturation and differentiation state of the NK cell compartment; moreover, NK cell differentiation is driven in part by exposure to infection. Pathogens can thus mould the NK cell response to maximise their own success and/or minimise the damage they cause. Here, we review recent evidence that pathogen-and vaccine-derived signals influence the differentiation, adaptation and subsequent effector function of human NK cells.

In Utero Activation of NK Cells in Congenital CMV Infection

“…The fetal immune system is uniquely prone towards tolerance in order to prevent fetal-maternal alloreactivity, which poses a challenge when viral infection occurs in utero. While NK cells play a critical 10 role in the host defense against CMV in adults, little is known about whether fetal NK cells can expand and react to viral infection in utero [26]. Because NK cells develop by gestational week 6 and are the dominant lymphocyte population in the fetal liver and lung, they are poised to play an important role in the fetal immune response [27,28].…”

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

“…In peripheral blood, two main subpopulations have been described; one cytotoxic CD3-CD56dim CD16high, and one cooperative or tolerogenic CD3-CD56bright CD16dim [1]. NK cells can be transformed from one type to another depending on tissue milieu, cytokine or receptor stimulation, or pharmacologic therapy [1,2]. However, NK activity modulation does not come solely by expressing CD16 and CD56 receptor.…”

“…A complex array of molecules are responsible for NK cell activity. There are activating or cytotoxic receptors, integrin, selectins, killing inhibitory receptors (KIR), PD-1 receptors, CD161, and cytokine receptors responsible for NK cell activity [1,2]. The expression of different receptors may be dependent on the stimulus or tissue milieu.…”

“…Reports of NK cells in innate immune response and memory events have led to a better understanding of NK cells' tissue-specific role in the immune response [2][3][4][5][6][7]. In a similar fashion as tissue macrophages, tissue-resident NK cells (trNK cells) differ in antigen expression and function.…”

New horizons for natural killer cell research in cancer, infection and inflammation

“…17 Here, the NK cell and vaccination experts, Goodier and Riley, revisit the biological regulation of human NK cells by pathogens and vaccines, and discuss how these events influence NK cell differentiation, thus causing adaptation of their effector functions. 18 Moving from vaccination to inflammation, an important aspect of NK cell biology is the additional pro-inflammatory effector function of NK cells, which can be the first and major producers of pro-inflammatory cytokines such as IFN-c and GM-CSF. 19 Although the appropriate secretion of such cytokines can be important to restore immunity and resolve infection, it can also contribute to exacerbated disease or overzealous/ deleterious inflammation.…”