Role of IL10 signaling in the circadian control of host response to Influenza infection

The circadian clock confers a time-of-day specific protection against influenza A Virus (IAV) infection by regulating the host response and limiting immunopathology. IL10 is a cytokine with significant immunoregulatory functions; however, the role of IL10 in IAV is unclear, with reports of both benefit and harm from its blockade early during the infection. Since the expression of IL10R shows diurnal rhythmicity in the lungs, we tested if IL10 signaling contributes to time-of-day specific protection against IAV. Overall design: Mice were intranasally infected with 30-35 PFU of mouse-adapted H1N1 (PR8) at either ZT11 or ZT23. To block IL-10 signaling, mice were treated with either IL-10R1a monoclonal antibody (Clone 1B1.3A, BioXCell BE0050) or polyclonal IgG (Clone MOPC-21, BioXCell BE0083) during the infection. Mice were treated with 100ug/10uL of IL10R1 MAb administered intranasally D0 in 10uL PBS, 150ug/100uL of IL10R1 Mab administered intraperitoneally on day 3 in 100uL of PBS, and 100ug/100uL of IL10R1 MAb administered i.p. D5.