Abstract
Rhinovirus (RV), the causative agent of the common cold, causes only mild upper respiratory tract infections in healthy individuals, but can cause longer lasting and more severe pulmonary infections in people with chronic lung diseases and in the setting of immune suppression or immune deficiency. RV-infected lung structural cells release type I interferon (IFN-I), initiating the immune response, leading to protection against viruses in conjunction with migratory immune cells. However, IFN-I release is deficient in some people with asthma. Innate immune cells, such as natural killer (NK) cells, are proposed to play major roles in the control of viral infections, and may contribute to exacerbations of chronic lung diseases, such as asthma. In this study, we characterized the NK cell response to RV infection using an in vitro model of infection in healthy individuals, and determined the extent to which IFN-I signaling mediates this response. The results indicate that RV stimulation in vitro induces NK cell activation in healthy donors, leading to degranulation and the release of cytotoxic mediators and cytokines. IFN-I signaling was partly responsible for NK cell activation and functional responses to RV. Overall, our findings suggest the involvement of NK cells in the control of RV infection in healthy individuals. Further understanding of NK cell regulation may deepen our understanding of the mechanisms that contribute to susceptibility to RV infections in asthma and other chronic lung diseases.
Highlights
Respiratory viruses, rhinoviruses (RV), typically cause only mild, self-limited infections in healthy individuals, but the consequences of infection can be much more serious in people with chronic lung diseases and in the setting of immune suppression or immune deficiency (Glezen et al, 2000; Versluys et al, 2010; Costa et al, 2011; Jacobs et al, 2013)
To determine whether RV could activate natural killer (NK) cells, and the extent to which NK cell activation and functional changes are IFN-I dependent, Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were cultured for 1 h in the presence or absence of B18R to block IFN-I signaling, prior to culture for 24 h in the presence or absence of RV16 stimulation
Our results demonstrate that neither RV16 stimulation, nor blocking of IFN-I signaling, altered the frequency of lymphocytes (Figure 1A), though RV16 induced a small increase in CD56+ NK cell frequency that was less apparent when IFN-I signaling was blocked (Figure 1B)
Summary
Respiratory viruses, rhinoviruses (RV), typically cause only mild, self-limited infections in healthy individuals, but the consequences of infection can be much more serious in people with chronic lung diseases and in the setting of immune suppression or immune deficiency (Glezen et al, 2000; Versluys et al, 2010; Costa et al, 2011; Jacobs et al, 2013). Asthmatics are no Frontiers in Cellular and Infection Microbiology | www.frontiersin.org van der Heide et al. IFN-I Signaling Involved in NK Cell Response to RV more likely than healthy individuals to develop a cold, but are substantially more likely for the infection to spread to the lower respiratory tract, causing more severe symptoms (Corne et al, 2002). IFN-I Signaling Involved in NK Cell Response to RV more likely than healthy individuals to develop a cold, but are substantially more likely for the infection to spread to the lower respiratory tract, causing more severe symptoms (Corne et al, 2002) This raises important questions regarding the mechanisms by which healthy people are able to mount an effective host response to RV. Understanding these processes that occur in healthy individuals might help to explain why RV infections can have such severe outcomes in people with asthma
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