Adaptive reconfiguration of the human NK-cell compartment in response to cytomegalovirus: A different perspective of the host-pathogen interaction

IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
European Journal of Immunology (Impact Factor: 4.03). 05/2013; 43(5). DOI: 10.1002/eji.201243117
Source: PubMed


As discussed in this review, human cytomegalovirus (HCMV) infection in healthy individuals is associated with a variable and persistent increase of NK cells expressing the CD94/NKG2C activating receptor. The expansion of NKG2C(+) NK cells reported in other infectious diseases is systematically associated with HCMV co-infection. The functionally mature NKG2C(bright) NK-cell subset expanding in HCMV(+) individuals displays inhibitory Ig-like receptors (KIR and LILRB1) specific for self HLA class I, and low levels of NKp46 and NKp30 activating receptors. Such reconfiguration of the NK-cell compartment appears particularly marked in immunocompromised patients and in children with symptomatic congenital infection, thus suggesting that its magnitude may be inversely related with the efficiency of the T-cell-mediated response. This effect of HCMV infection is reminiscent of the pattern of response of murine Ly49H(+) NK cells against murine CMV (MCMV), and it has been hypothesized that a cognate interaction of the CD94/NKG2C receptor with HCMV-infected cells may drive the expansion of the corresponding NK-cell subset. Yet, the precise role of NKG2C(+) cells in the control of HCMV infection, the molecular mechanisms underlying the NK-cell compartment redistribution, as well as its putative influence in the response to other pathogens and tumors remain open issues.

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Available from: Aura Muntasell, Oct 16, 2014
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    • "The role for lower affinity interactions between NKG2C and HLA-E-peptide complexes is less clear, although it has been proposed that a stable complex of HLA-E with a CMV nonamer peptide from the orf UL40 protein may activate NKG2C (Heatley et al. 2013; Muntasell et al. 2013). Intriguingly, HLA-E polymorphisms have been associated with the development of psoriasis lesions and decreased frequencies of NKG2C þ NK cells (Batista et al. 2013; Patel et al. 2013; Zeng et al. 2013). "
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