Abstract

Abstract Respiratory viral infections, including parainfluenza virus (PIV), are a significant cause of illness and death worldwide, especially among young children and the elderly. Understanding the immune response to these viruses is important for reducing pathology and developing vaccines. As a first line of defense, Natural Killer (NK) cells provide critical host protection against viruses. Their presence in the lung, a key site of pathogen entry, suggests an important role for these cells in respiratory viral infection. Sendai virus (SeV), a natural mouse pathogen, is closely related to human PIV, and causes respiratory infection similar to that seen in humans. No studies have directly assessed NK cells in host protection during SeV infection. Our research shows that NK cells are recruited into the lung airways by day 2 post infection (p.i.), and continue to accumulate in the lungs. NK-depleted mice have higher viral titers in the lungs on days 3 and 5 p.i. NK cells upregulate the activating receptor NKG2D during infection, and in the absence of NK cells, a higher percentage of CD8 T cells expresses NKG2D. NKG2D antibody blockade results in higher viral titers on day 4 p.i. Our data show that NK cells play a protective role and are an important cell population during PIV infection. These studies will deepen our understanding of NK cell biology, and may also help in the design of new methods to treat, and possibly prevent, these diseases.

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