Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections

Lee, Sanghyun; Baldridge, Megan T.

| Effects of interferon-lambda (IFN-λ) on viruses in the intestine. Upon intestinal viral infection, viral RNA is sensed by pattern-recognition receptors, RIG-I, MDA5, and NLRP6, which signal through mitochondria-or peroxisome-associated MAVS to stimulate transcription of type I and III IFN by IRF3/IRF7 and IRF1. IFN-λ is produced by intestinal epithelial cells (IECs) and possibly immune cells in the intestine. IFN-λ signaling through the IFN-λ-receptor (IFNλR) on IECs stimulates production of antiviral effectors, or interferon-stimulated genes (ISGs), via STAT1/STAT2/IRF9-mediated transcription. IFN-λ thus serves to regulate viral levels in the intestine. IFN-λ can interact with IL-22, whose receptor is expressed on IECs (IL22R), to coordinately regulate viral infection, and in some settings may also interact with type I IFNs, which signal through IFNαR. IFN-λ has also been shown to play a role in influencing interactions between commensal bacteria and enteric viral pathogens. (13) . Intestinal epithelial cells (IECs) produce type III IFNs with in vivo viral infection (14) (15) (16) . However, leukocytes generate IFN-λ in vitro (10, 17) , and intestinal eosinophils (18) and plasmacytoid dendritic cells (pDCs) (19) can produce IFN-λ in vivo, suggesting the possibility of additional cellular IFN-λ contributors.