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Different expression of DNAM-1 and TIGIT on CD56dimCd16+ and CD56brightCD16- NK cell population in patients with hemorrhagic fever with renal syndrome

Hemorrhagic fever with renal syndrome (HFRS) is a multisystemic disease caused by hantaviruses (HTV). Immune response is involved in HFRS pathogenesis. Natural killer (NK) cells are found to be activated during HFRS infection. Data regarding their immunological interaction with infected cells are still scarce. NK cells posses a variety of activating and inhibitory receptors sensing potential threats in their environment and engaging their effector function. DNAM-1, an activating receptor, is important for formation of immunological synapses, cytokines secretion and differentiation of NK cells into memory cells. TIGIT, on the other hand, exhibits immunomodulatory function by competing with DNAM-1 for binding to their shared ligands on target cells: CD155 and CD112. The fine tuned balance between this receptors is crucial to achieve the appropriate immune response. Our aim was to explore the dynamics of DNAM-1 and TIGIT expression on NK cells in PUUV infected patients. Blood samples were collected from 14 male patients at two stages of disease, early (upon hospitalization) and late at discharge. Expression of DNAM-1 and TIGIT were analyzed using flow cytometry on CD56dimCD16+ (predominate, more educated population) and CD56brigtCD16- NK cells. Expression in HFRS patients were compared with healthy, age and sex matched controls (n=9). Percentage of CD56dimCD16+ was significantly decreased in early stage of disease, reaching the level of healthy controls at discharge. On the contrary, CD56brigthCD16- cells were significantly increased in early stage of disease. Median fluorescence intensity of DNAM-1 receptor on CD56dimCD16+ population was significantly increased in both stages of disease, compared to healthy controls, as well as on CD56brightCD16- cells. Interestingly, in the late HFRS phase DNAM-1 was significantly higher on CD56brightCD16- cells compared to early stage. Expression of TIGIT was significantly increased in both NK cell population during the course of disease. Different expression of activating receptor DNAM-1 and inhibitory TIGIT on NK cell population could play an important role in managing and directing early immune response to HTV infection in order to avoid excessive activation upon recognition of target cells.

natural killer cells ; DNAM-1 ; TIGIT

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