Differential mucosal IL‐10‐induced immunoregulation of innate immune responses occurs in influenza infected infants/toddlers and adults

Young children (<5 years of age but especially those <2‐year old) exhibit high rates of morbidity and frequently require hospitalizations due to complications from respiratory viral infections. This is also a population for which we understand less about how their unique level of immunological maturation affects their antiviral immune responses. However, we do know from prior studies that their T cells appear to apoptose in the lungs owing to limited interferon (IFN)γ autocrine signaling during infection. To begin to further understand additional limits, we utilized an infant/toddler murine model infected with influenza virus with an adult comparator. In our model, young mice exhibited lower interleukin (IL)‐10 + IFNγ + co‐producing CD4 T cells infiltrating the lungs that paralleled with a failed switch from an innate to adaptive immune response at the mid infection stage. Specifically, limited co‐IL‐10 production correlated with a lack of influenza‐specific antibodies and subsequent complement receptor signaling (complement receptor type‐1 related gene Y (CCRY)/p65) to the lung infiltrating CD4 T cells therefore limiting their IKAROs upregulation. Thus, limited IL‐10 production appeared to diminish signaling to lung macrophages to stop accumulating late into infection. Taken together, our results suggest a novel role for complement mediated signaling in CD4 T cells with respect to IL‐10 co‐production. Furthermore, a subsequent failure to shift from the unfocused innate immune response to the specific adaptive responses may be a principle cause in the enhanced morbidity common in respiratory viral infection of young children.