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

Department

Research

Document Type

Article

Publication Title

Immunology and Cell Biology

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)-10IFNγ 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.

First Page

252

Last Page

260

DOI

10.1038/icb.2016.91

Volume

95

Issue

3

Publication Date

3-1-2017

Medical Subject Headings

Aging (pathology); Animals; Antibody Specificity (immunology); CD4-Positive T-Lymphocytes (immunology); Feedback, Physiological; Female; Ikaros Transcription Factor (metabolism); Immunity, Innate; Interferon-gamma; Interleukin-10 (blood, metabolism); Kinetics; Lymphocyte Activation (immunology); Macrophages (pathology); Male; Mice; Mice, Inbred C57BL; Mucous Membrane (immunology, virology); Orthomyxoviridae Infections (immunology, pathology, virology); Positive Regulatory Domain I-Binding Factor 1 (metabolism); Receptors, Complement (metabolism)

PubMed ID

27629065

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