Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections

Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2016-04, Vol.12 (4), p.e1005600-e1005600
Main Authors: Lin, Jian-Da, Feng, Ningguo, Sen, Adrish, Balan, Murugabaskar, Tseng, Hsiang-Chi, McElrath, Constance, Smirnov, Sergey V, Peng, Jianya, Yasukawa, Linda L, Durbin, Russell K, Durbin, Joan E, Greenberg, Harry B, Kotenko, Sergei V
Format: Article
Language:English
Subjects:
Analysis
Animals
Animals, Newborn
B cells
Biology and Life Sciences
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Experiments
Feces
Humans
Immunoblotting
Immunohistochemistry
Infections
Interferon
Interferon Type I - immunology
Interferon-gamma - immunology
Intestines - immunology
Inventors
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Polymerase Chain Reaction
Rotavirus
Rotavirus infections
Rotavirus Infections - immunology
Small intestine
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type-specific IFN signaling, STAT1 and Rag2 to dissect distinct and overlapping contributions of type I and type III IFNs to protection against homologous murine (EW-RV strain) and heterologous (non-murine) simian (RRV strain) rotavirus infections in suckling mice. Experiments demonstrated that murine EW-RV is insensitive to the action of both types of IFNs, and that timely viral clearance depends upon adaptive immune responses. In contrast, both type I and type III IFNs can control replication of the heterologous simian RRV in the gastrointestinal (GI) tract, and they cooperate to limit extra-intestinal simian RRV replication. Surprisingly, intestinal epithelial cells were sensitive to both IFN types in neonatal mice, although their responsiveness to type I, but not type III IFNs, diminished in adult mice, revealing an unexpected age-dependent change in specific contribution of type I versus type III IFNs to antiviral defenses in the GI tract. Transcriptional analysis revealed that intestinal antiviral responses to RV are triggered through either type of IFN receptor, and are greatly diminished when receptors for both IFN types are lacking. These results also demonstrate a murine host-specific resistance to IFN-mediated antiviral effects by murine EW-RV, but the retention of host efficacy through the cooperative action by type I and type III IFNs in restricting heterologous simian RRV growth and systemic replication in suckling mice. Collectively, our findings revealed a well-orchestrated spatial and temporal tuning of innate antiviral responses in the intestinal tract where two types of IFNs through distinct patterns of their expression and distinct but overlapping sets of target cells coordinately regulate antiviral defenses against heterologous or homologous rotaviruses with substantially different effectiveness.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1005600