Type-I interferon modulates monocyte recruitment and maturation in chronic inflammation (94.4)

Abstract

Abstract Chronic inflammation is characterized by continuous recruitment and activation of immune cells such as monocytes in response to a persistent stimulus. Production of pro-inflammatory mediators by monocytes leads to tissue damage and perpetuates the inflammatory response. However, the mechanism(s) responsible for the sustained influx of monocytes in chronic inflammation are not well defined. In chronic peritonitis induced by 2,6,10,14-tetramethylpentadecane (TMPD; pristane), the persistent recruitment of Ly6Chi inflammatory monocytes into the peritoneum was abolished in type-I interferon (IFN-I) receptor deficient mice but was unaffected by the absence of IFN-γ, TNF-α, IL-6 or IL-1. IFN-I signaling stimulated the production of chemokines (CCL2, CCL7, and CCL12) that recruited Ly6Chi monocytes via interactions with the chemokine receptor CCR2. Interestingly, after TMPD treatment, the rapid turnover of inflammatory monocytes in the inflamed peritoneum was associated with a lack of differentiation into Ly6Clo monocytes/macrophages, a more mature subset with enhanced phagocytic capacity. In contrast, Ly6Chi monocytes/macrophages differentiated normally into Ly6Clo cells in IFN-I receptor deficient mice. The effects of IFN-I were specific for monocytes as granulocyte migration was unaffected in the absence of IFN-I signaling. Taken together, our findings reveal a novel role of IFN-I in promoting the recruitment of inflammatory monocytes via the chemokine receptor CCR2. Continuous monocyte recruitment and the lack of terminal differentiation induced by IFN-I may help sustain the chronic peritoneal inflammatory response.