title: Differential mucosal IL-10-induced immunoregulation of innate immune responses occurs in influenza infected infants/toddlers and adults.
abstract: 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.
authors.affiliation: Rochester Research Institute, Rochester General Hospital, Rochester, NY, USA.|Department of Biomedical Sciences, Iowa State University, Biomedical Sciences, Ames, IA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Verhoeven
authors.affiliation: Rochester Research Institute, Rochester General Hospital, Rochester, NY, USA.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Perry
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D025461:Feedback, Physiological; D005260:Female; D051740:Ikaros Transcription Factor / Q000378:metabolism; D007113:Immunity, Innate; D007371:Interferon-gamma; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology* / Q000821:virology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D000074462:Positive Regulatory Domain I-Binding Factor 1 / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism
chemical_list: C513258:Prdm1 protein, mouse; D011951:Receptors, Complement; C497238:Zfpn1a1 protein, mouse; D016753:Interleukin-10; D051740:Ikaros Transcription Factor; D007371:Interferon-gamma; D000074462:Positive Regulatory Domain I-Binding Factor 1