16/11/2010 - General information
This study was published at the end of October in the online edition of the journal Blood
A study directed by Miguel López-Botet, director of the IMIM (Hospital del Mar Research Institute) and coordinator of the Immunology Laboratory of the Health and Experimental Science Department (CEXS), has identified the receptors involved in triggering the cytotoxic activity of human NK (natural killer) cells in response to human cytomegalovirus (HCMV)-infected dendritic cells. The study was pre-published in the online edition of the journal Blood at the end of October.
The study developed by Giuliana Magri, main researcher and doctoral candidate at the Immunology Laboratory of the CEXS Department, shows for the first time that NK cells can recognise, activate themselves and kill the HCMV-infected dendritic cells, overcoming the immune evasion mechanisms developed by the virus.
What strengthens this study, which has been developed as part of a European Marie Curie programme, in collaboration with various researchers in Italy, Germany and the USA, is the fact that, for the first time ever, the ability of human NK cells to respond to HCMV-infected dendritic cells in an autologous system has been demonstrated and the receptors identified, contributing extremely valuable information about the HCMV infection.
In fact, the authors of the study developed a human dendritic cell HCMV infection model and the subsequent in vitro co-culture of these infected cells and purified NK cells from the blood of the same individual. Using this experimental system, the authors were able to assess the consequences of the interaction between the two cells and were able to identify the Nkp46 and DNAM-1 receptors as the NK cell receptors which trigger the cytolytic mechanism which kills HCMV-infected dendritic cells.
In the immune system, NK cells are specialised in recognising and eliminating cells infected by various pathogens. These cells contain cytotoxic granules which are released and kill the infected cell. Thus, NK cells play a direct part in controlling the first stages of infections, as well as modulating the development of the adaptive phase of the immune response by secreting pro-inflammatory cytokines.
An infection which often goes unnoticed
Human cytomegalovirus (HCMV) is a virus of the Herpesviruses group with a high prevalence, to the point that 85% of the adult population is infected by HCMV.
In healthy individuals, the immune system can control the cytomegalovirus infection, despite the many strategies developed by the virus to avoid being controlled. The outcome of the complex relationship established between the virus and the immune system is the acquisition of a persistent infection, which has alternating periods of latency and reactivation of the virus lytic cycle, which generally go unnoticed clinically.
An infection which becomes serious in certain cases
Nevertheless, in immunocompromised individuals, such as in the case of patients who receive immunosuppressive treatment as a result of a transplant, in AIDS patients or in congenital HCMV infections, cytomegalovirus infections generate serious illnesses. Furthermore, chronic HCMV infection has been associated with the ageing of the immune system and is considered to be a risk factor in inflammatory diseases such as atherosclerosis.
Giuliana Magri, Aura Muntasell, Neus Romo, Andrea Sáez-Borderías, Daniela Pende, Daniel E. Geraghty, Hartmut Hengel, Ana Angulo, Alessandro Moretta and Miguel López-Botet (2010), " NKp46 and DNAM-1 NK cell receptors drive the response to human cytomegalovirus infected myeloid dendritic cells overcoming viral immune evasion strategies", Blood, prepublished online October 28, 2010; DOI 10.1182/blood-2010-08-301374.