TLR/NCR/KIR: Which One to Use and When?

Simona Sivori,Simona Carlomagno,Silvia Pesce,Alessandro Moretta,Massimo Vitale,Emanuela Marcenaro

doi:10.3389/fimmu.2014.00105

Abstract

By means of a complex receptor array, Natural killer (NK) cells can recognize variable patterns of ligands and regulate or amplify accordingly their effector functions. Such NK receptors include old, rather conserved, molecules, such as toll-like receptors (TLRs), which enable NK cells to respond both to viral and bacterial products, and newer and evolving molecules, such as killer Ig-like receptors and natural cytotoxicity receptors, which control NK cytotoxicity and are responsible for the elimination of virus-infected or tumor cells without damaging self-unaltered cells. In addition, to rapidly gain new functions NK cells also can acquire new receptors by trogocytosis. Thus, NK cells may have adapted their receptors to different functional needs making them able to play a key role in the modulation of critical events occurring in several compartments of human body (primarily in SLCs but also in decidua during pregnancy). In this review, we will discuss on how the various types of receptors can be used to address specific functions in different immunological contexts.

Highlights

Natural killer (NK) cells are innate lymphocytes present in all mammalian species capable of mediating multiple effector functions
Several data have demonstrated that the different NK cell receptors can reciprocally coordinate and regulate their functions, contributing to the initiation of innate responses and to the subsequent priming of adaptive immune responses
NK cell activation may be mediated by the engagement of toll-like receptors (TLRs) and/or natural cytotoxicity receptors (NCRs), two different types of receptors that may cooperate in inducing NK cell triggering, and in controlling viral/bacterial infection and cancer

Summary

INTRODUCTION

Natural killer (NK) cells are innate lymphocytes present in all mammalian species capable of mediating multiple effector functions. The CD56bright NK cell subset presents little cytolytic activity but releases high amounts of cytokines, whereas CD56dim NK cell subset displays potent cytotoxicity and high cytokine production in response to specific stimuli [4,5,6] The former subset is characterized by the CD16−KIR−NKG2A+ phenotype and largely predominates in lymph nodes, according to the expression of CCR7 (the homing receptor for secondary lymphoid compartments, SLCs) [7, 8], whereas the latter subset is CD16+KIR+ and/or NKG2A+ and prevails in peripheral blood and inflamed tissues where they can be recruited, thanks to the expression of the CXCR1, CX3CR1, and ChemR23 chemokine receptors [4, 9, 10].

CpG DNA motifs

CONCLUSION