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

Gimeno Brias, Silvia, Marsden, Morgan, Forbester, Jessica, Clement, Mathew ORCID: https://orcid.org/0000-0002-9280-5281, Brandt, Cordelia, Harcourt, Katherine, Kane, Leanne, Chapman, Lucy, Clare, Simon and Humphreys, Ian R. ORCID: https://orcid.org/0000-0002-9512-5337 2018. 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 13 (5) , e0197596. 10.1371/journal.pone.0197596

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Public Library of Science
ISSN:	1932-6203
Funders:	Wellcome Trust
Date of First Compliant Deposit:	21 May 2018
Date of Acceptance:	4 May 2018
Last Modified:	22 Oct 2023 10:47
URI:	https://orca.cardiff.ac.uk/id/eprint/111607

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