The evolutionary arms race between NK cells and viruses: Who gets the short end of the stick?

Abstract

NK cells in viral infectionsNK cells are innate cytotoxic lymphocytes essential for the control of a broad range of viral infections. The activation and function of NK cells are based on a tightly regulated interplay between inhibitory and activating signals induced by the receptors expressed on their surface (reviewed in [1]) or by a variety of cytokines generated by the interaction between NK cells and other innate immune cells, such as macrophages and DCs [2,3]. Type I IFNs, IL-12, IL-15, and IL-18 produced by macrophages and DCs are indispensable for NK-cell maturation and regulation of NK-cell function. More recently, it has been demonstrated that TGF-β signaling limits the maturation dynamics of NK cells during the neonatal period [4]. Mice lacking the TGF-β receptor on the surface of their NK cells and DCs possess more mature NK cells and can therefore control viral infection more efficiently compared with control mice [4], providing an explanation for the deficient NK-cell response early in life.Correspondence: Prof. Stipan Jonjić e-mail: stipan.jonjic@medri.uniri.hrThe impact of NK cells on virus control has been proven to play a key role in different infection models including those modeling infection with influenza virus, HIV, HCV, coxsackievirus, and poxviruses. Arguably, the role of NK cells in the control of herpesviruses, especially CMV, has been most widely studied up till now (reviewed in [5][6][7]). Upon activation and recruitment to the site of infection, NK cells use several mechanisms to limit virus replication: (i) a cytolytic response involving the secretion of cytolytic granules (granzymes and perforin) upon engagement of an activating receptor [8,9], (ii) production of pro-inflammatory cytokines with antiviral activity such as , (iii) killing of target cells via FasL or TRAIL [11], and (iv) Abdependent, cell-mediated cytotoxicity-mediated lysis via CD16 [12].Besides their well-recognized role in the control of virus replication, NK cells have been shown to possess additional functions that can be beneficial or detrimental to the host. For instance, decidual NK cells are considered to be important for placentation and maintenance of materno-fetal immune tolerance [13], but there is a very limited amount of data published on the role of NK cells in the control of infections during pregnancy. In mouse cytomegalovirus (MCMV)-infected mice, NK cells preserve the integrity and function of the salivary gland, an organ that iswww.eji-journal.eu 868Antonija Miletić et al. Eur. J. Immunol. 2013. 43: 867-877 important for horizontal virus spread [14,15]. A study using the mouse model of salivary gland dysfunction after an acute MCMV infection showed the involvement of NK cells in the prevention of acinar atrophy and loss of secretions [16]. Conversely, the NK-cell response could play a negative role in virus infection, as demonstrated in the case of infection with RSV [17]. NK cells accumulate in the lungs of BALB/c mice at the early stage of RSV infection, where they gain an activated phenotyp...

Expression, Function, and Molecular Properties of the Killer Receptor Ncr1-Noé

“…The results presented in the present study were supported by additional works demonstrating that Ncr1 indeed plays no role in MCMV infection (36) and in decidual human NK recognition of human CMV (44).…”

“…1C). We selected these three strains because past work using depleting Abs against NK cells demonstrated that NK cell function was critical for controlling MCMV infection in all three strains (34)(35)(36)(37).…”

Recruitment of activating NK‐cell receptors 2B4 and NKG2D to membrane microdomains in mammalian cells is dependent on their transmembrane regions

“…NK cells are large, granular lymphocytes of the innate immune system that contribute to successful immune responses by killing virally infected or transformed cells and by producing various cytokines [1][2][3]. The function of NK cells is controlled by the integration of signals from activating and inhibitory surface receptors Membrane microdomains, also called lipid rafts, are defined as cholesterol-and sphingolipid-rich membrane domains that affect various cellular functions, such as signaling, protein sorting, or endocytosis [9,10].…”

“…However, either interfering with the association between NKG2D and DAP10, or mutating the transmembrane region of 2B4 impacted the recruitment of the receptors to detergentresistant membrane fractions and modulated the function of 2B4 in NK cells. Our data suggest a potential interaction between the transmembrane region of NK-cell receptors and membrane lipids as a molecular mechanism involved in determining the membrane confinement of activating NK-cell receptors.Keywords: 2B4 r Activating receptor r Lipid rafts r Membrane microdomains r NK cells r NKG2D r Signal transduction Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction NK cells are large, granular lymphocytes of the innate immune system that contribute to successful immune responses by killing virally infected or transformed cells and by producing various cytokines [1][2][3]. The function of NK cells is controlled by the integration of signals from activating and inhibitory surface receptors Correspondence: Prof. Carsten Watzl e-mail: watzl@ifado.de [4].…”

“…Keywords: 2B4 r Activating receptor r Lipid rafts r Membrane microdomains r NK cells r NKG2D r Signal transduction Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction NK cells are large, granular lymphocytes of the innate immune system that contribute to successful immune responses by killing virally infected or transformed cells and by producing various cytokines [1][2][3]. The function of NK cells is controlled by the integration of signals from activating and inhibitory surface receptors Correspondence: Prof. Carsten Watzl e-mail: watzl@ifado.de [4].…”