Interferon lambda is required for interferon gamma-expressing NK cell responses but does not afford antiviral protection during acute and persistent murine cytomegalovirus infection

PloS One
Silvia Gimeno BriasIan R Humphreys

Abstract

Interferon lambda (IFNλ) 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 IFNλ restricts in vitro replication of the β-herpesvirus murine cytomegalovirus (mCMV). However, IFNλR1-deficient (Ifnλr1-/-) 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 IFNλ influences NK cell responses during mCMV infection. Ifnλr1-/- mice exhibited defective development of conventional interferon-gamma (IFNγ)-expressing NK cells in the spleen during mCMV infection whereas accumulation of granzyme B-expressing NK cells was unaltered. In vitro, development of splenic IFNγ+ NK cells following stimulation with IL-12 or, to a lesser extent, IL-18 was abrogated by IFNλR1-deficiency. Thus, IFNλ 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.

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Citations

Jan 11, 2020·Frontiers in Immunology·Caroline L AshleyBarry Slobedman
Jan 6, 2021·Virologica Sinica·Yue Yin, Herman W Favoreel
Mar 9, 2021·Frontiers in Immunology·Kellen J CavagneroTaylor A Doherty
Aug 27, 2021·Blood·Andrea S HendenGeoffrey R Hill

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Methods Mentioned

BETA
Knockout
Assay
ELISAs
reverse transcription PCR
flow
ELISA
flow cytometry

Software Mentioned

FlowJo
FACS Diva

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