Decreased production of epithelial-derived antimicrobial molecules at mucosal barriers during early life

Young age is a risk factor for respiratory and gastrointestinal infections. Here, we compared infant and adult mice to identify age-dependent mechanisms that drive susceptibility to mucosal infections during early life. Transcriptional profiling of the upper respiratory tract (URT) epithelium reveal...

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Bibliographic Details
Published in:Mucosal immunology 2021-11, Vol.14 (6), p.1358-1368
Main Authors: Lokken-Toyli, Kristen L, de Steenhuijsen Piters, Wouter A A, Zangari, Tonia, Martel, Rachel, Kuipers, Kirsten, Shopsin, Bo, Loomis, Cynthia, Bogaert, Debby, Weiser, Jeffrey N
Format: Article
Language:English
Subjects:
Age
Age Factors
Animals
Anti-Infective Agents - metabolism
Antimicrobial agents
Antimicrobial Peptides - biosynthesis
Biomarkers
Disease Resistance
Enzymatic activity
Epithelial Cells - metabolism
Epithelium
Gastrointestinal tract
Gene Expression Regulation
Humans
Immunity, Innate
Immunity, Mucosal
Immunoglobulin A
Immunohistochemistry
Infants
Lactoferrin
Lysozyme
Mice
Mucosa
Mucous Membrane - immunology
Mucous Membrane - metabolism
Muramidase - biosynthesis
Muramidase - genetics
Organ Specificity
Respiratory tract
Risk factors
Small intestine
Streptococcus infections
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Summary:Young age is a risk factor for respiratory and gastrointestinal infections. Here, we compared infant and adult mice to identify age-dependent mechanisms that drive susceptibility to mucosal infections during early life. Transcriptional profiling of the upper respiratory tract (URT) epithelium revealed significant dampening of early life innate mucosal defenses. Epithelial-mediated production of the most abundant antimicrobial molecules, lysozyme, and lactoferrin, and the polymeric immunoglobulin receptor (pIgR), responsible for IgA transcytosis, was expressed in an age-dependent manner. This was attributed to delayed functional development of serous cells. Absence of epithelial-derived lysozyme and the pIgR was also observed in the small intestine during early life. Infection of infant mice with lysozyme-susceptible strains of Streptococcus pneumoniae or Staphylococcus aureus in the URT or gastrointestinal tract, respectively, demonstrated an age-dependent regulation of lysozyme enzymatic activity. Lysozyme derived from maternal milk partially compensated for the reduction in URT lysozyme activity of infant mice. Similar to our observations in mice, expression of lysozyme and the pIgR in nasopharyngeal samples collected from healthy human infants during the first year of life followed an age-dependent regulation. Thus, a global pattern of reduced antimicrobial and IgA-mediated defenses may contribute to increased susceptibility of young children to mucosal infections.
ISSN:1933-0219
1935-3456
DOI:10.1038/s41385-021-00438-y