Title: Impaired Tumor-Necrosis-Factor-α-driven Dendritic Cell Activation Limits Lipopolysaccharide-Induced Protection from Allergic Inflammation in Infants.
Authors: Bachus, Holly; Kaur, Kamaljeet; Papillion, Amber M; Marquez-Lago, Tatiana T; Yu, Zhihong; Ballesteros-Tato, André; Matalon, Sadis; León, Beatriz
Published In Immunity, (2019 01 15)
Abstract: Infants have a higher risk of developing allergic asthma than adults. However, the underlying mechanism remains unknown. We show here that sensitization of mice with house-dust mites (HDMs) in the presence of low-dose lipopolysaccharide (LPS) prevented T helper 2 (Th2) cell allergic responses in adult, but not infant, mice. Mechanistically, adult CD11b+ migratory dendritic cells (mDCs) upregulated the transcription factor T-bet in response to tumor necrosis factor-α (TNF-α), which was rapidly induced after HDM + LPS sensitization. Consequently, adult CD11b+ mDCs produced interleukin-12 (IL-12), which prevented Th2 cell development by promoting T-bet upregulation in responding T cells. Conversely, infants failed to induce TNF-α after HDM + LPS sensitization. Therefore, CD11b+ mDCs failed to upregulate T-bet and did not secrete IL-12 and Th2 cell responses normally developed in infant mice. Thus, the availability of TNF-α dictates the ability of CD11b+ mDCs to suppress allergic Th2-cell responses upon dose-dependent endotoxin sensitization and is a key mediator governing susceptibility to allergic airway inflammation in infant mice.
PubMed ID: 30635238
MeSH Terms: Adult; Animals; Animals, Newborn; Antigens, Dermatophagoides; Cell Differentiation; Dendritic Cells/physiology*; Humans; Hypersensitivity/immunology*; Immunization; Infant; Inflammation/immunology*; Lipopolysaccharides/immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Pyroglyphidae/immunology; T-Box Domain Proteins/metabolism; Th2 Cells/immunology*; Tumor Necrosis Factor-alpha/metabolism*