NK-cells are involved in thymic atrophy induced by influenza A virus infection

Abstract

NK-cells have traditionally been viewed as innate effector lymphocytes that serve as a first line of defence against a range of viruses and tumours. More recently, the importance of NK-cell immunoregulatory functions has been highlighted. NK-cells can inhibit antiviral T-cell responses, and also play an important role in controlling harmful T-cell activity in autoimmunity and transplantation settings. Moreover, immunopathological effects of NK-cells during infection have been reported. Nevertheless, the phenotype and function of NK-cells in the thymus during influenza virus infection is not understood. In the present study, we demonstrated that influenza A virus (IAV) infection in mice led to severe thymic atrophy caused by increased thymic T-cell apoptosis and suppressed proliferation. We found that NK-cells played a critical role in this phenotype. IFN-c production by NK-cells was a contributing factor for thymic atrophy during IAV infection. Taken together, our data indicate that NK-cells are involved in the thymic atrophy associated with IAV infection.

Acute Thymic Involution and Mechanisms for Recovery

“…Because conducting research investigations on the thymuses of HIV-infected humans (Verinaud et al 2004) is difficult, many animal model systems have been developed. The simian immunodeficiency virus (SIV)-infected monkey model is much better than the feline and murine models, on the basis that this species not only acts as a natural host for the infection, but also offers Duan et al 2015;Hu et al 2016;Liu et al 2014 Parasites…”

“…This investigation explored the phenotype and immunological functions of natural killer (NK) cells and demonstrated that production of interferon (IFN)-γ by the NK cells caused the involution of thymus during the course of an IAV infection (Duan et al 2015). Similarly, influenza A virus type H1N1pmd09 infection induced severe ATI and depletion of the DP cells as a result of apoptosis.…”

“…In contrast, ATI is usually seen during gestational (Ekin et al 2016;Jacques et al 2014Jacques et al , 2015 and neonatal life (Eriksen et al 2014;Nickels et al 2015;Toti et al 2000) in humans. However, ATI in experimental animal models has been reported to occur not only during gestational periods (Kunzmann et al 2010;between ATI in adult experimental subjects and ageassociated thymic atrophy during the mid-phase of life in human beings is that the former occurs due to an increase in the death of thymocytes and has the ability to recover after the removal of the insult (Duan et al 2015;Lee et al 2011;Park et al 2007), whereas the latter is characterized by the substitution of lymphoid tissue with fat (adipose tissue) in a progressive time-dependent manner (Bodey et al 1997;Henry and Anderson 1987;Quaglino et al 2014). ATI is a common and well-known feature in various fungal Mendes-Giannini et al 2008;Souto et al 2003), viral (Duan et al 2015;Falkenberg et al 2014;Gao et al 2015) and bacterial infectious diseases (LeyvaRangel et al 2015;Ross et al 2012;Savino 2006).…”

“…However, ATI in experimental animal models has been reported to occur not only during gestational periods (Kunzmann et al 2010;between ATI in adult experimental subjects and ageassociated thymic atrophy during the mid-phase of life in human beings is that the former occurs due to an increase in the death of thymocytes and has the ability to recover after the removal of the insult (Duan et al 2015;Lee et al 2011;Park et al 2007), whereas the latter is characterized by the substitution of lymphoid tissue with fat (adipose tissue) in a progressive time-dependent manner (Bodey et al 1997;Henry and Anderson 1987;Quaglino et al 2014). ATI is a common and well-known feature in various fungal Mendes-Giannini et al 2008;Souto et al 2003), viral (Duan et al 2015;Falkenberg et al 2014;Gao et al 2015) and bacterial infectious diseases (LeyvaRangel et al 2015;Ross et al 2012;Savino 2006). ATI can also be caused by immune suppression (Billard et al 2011;Zhou et al 2016), hunger (Gavia-García et al 2015;Savino et al 2007), chemotherapy, radiography (DeBo et al 2015;Lynch et al 2009), pregnancy (Ekin et al 2016;Jacques et al 2014Jacques et al , 2015, transplant rejection (Gracia-Ahufinger et al 2015;Krenzien et al 2015) and other severe disease conditions (Wang et al 2016).…”

Influenza virus matrix protein M1 interacts with SLD5 to block host cell cycle

“…The mouse-adapted influenza A/Puerto Rico/8/34 (H1N1; PR8) virus was propagated as described previously (Duan et al, 2015;Zhou et al, 2016). 100 IU/ml penicillin, and 100 μg/ml streptomycin (Invitrogen).…”