Interferon Lambda Is Required For Interferon Gamma- Expressing Nk Cell Responses But Does Not Afford Antiviral Protection During Acute And Persistent Murine Cytomegalovirus Infection

Interferon lambda (IFN lambda)is a group of cytokines that belong to the IL-10 family. They exhibit antiviral activities against certain viruses during infection of the liver and mucosal tissues. Here we report that IFN lambda restricts in vitro replication of the beta-herpesvirus murine cytomegalovirus (mCMV). However, IFN lambda R1-deficient (Ifn lambda r1(-/-)) mice were not preferentially susceptible to mCMV infection in vivo during acute infection after systemic or mucosal challenge, or during virus persistence in the mucosa. Instead, our studies revealed that IFN lambda influences NK cell responses during mCMV infection. Ifn lambda r1(-/-) mice exhibited defective development of conventional interferon-gamma (IFN gamma)-expressing NK cells in the spleen during mCMV infection whereas accumulation of granzyme B-expressing NK cells was unaltered. In vitro, development of splenic IFN gamma(+) NK cells following stimulation with IL-12 or, to a lesser extent, IL-18 was abrogated by IFN lambda R1-deficiency. Thus, IFN lambda regulates NK cell responses during mCMV infection and restricts virus replication in vitro but is redundant in the control of acute and persistent mCMV replication within mucosal and non-mucosal tissues.