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Risk of repeated Moraxella catarrhalis colonization is increased in children with Toll-like receptor 4 Asp299Gly

Juho Vuononvirta1, Ville Peltola, Jussi Mertsola

  • 1From the *Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare; †Department of Pediatric, Turku University Hospital; and ‡Turku Institute for Child and Youth Research, University of Turku, Turku, Finland.

The Pediatric Infectious Disease Journal
|October 22, 2013
PubMed
Abstract

Insights

Finnish children with the Toll-like receptor (TLR) 4 Asp299Gly gene variant show a significantly higher risk of repeated Moraxella catarrhalis colonization. This genetic variation impacts innate immunity, increasing susceptibility to this common respiratory pathogen.

Area of Science:

  • Immunology
  • Pediatrics
  • Microbiology

Background:

  • Moraxella catarrhalis is a frequent cause of pediatric respiratory infections, including acute otitis media.
  • Toll-like receptor (TLR) 4 plays a crucial role in the human innate immune response.
  • The TLR4 Asp299Gly polymorphism is associated with a diminished response to Gram-negative bacterial lipopolysaccharides.

Purpose of the Study:

  • To investigate the association between the TLR4 Asp299Gly polymorphism and the risk of M. catarrhalis colonization in young Finnish children.
  • To determine if carrying the TLR4 Asp299Gly variant increases susceptibility to M. catarrhalis during the first two years of life.

Main Methods:

  • A prospective cohort study was conducted in Turku, Finland, involving 161 children.
  • Nasopharyngeal specimens were collected at 2, 12, and 24 months of age.
  • Bacterial identification used semiquantitative culture, and TLR4 Asp299Gly detection utilized pyrosequencing.

Main Results:

  • The prevalence of M. catarrhalis increased with age, reaching 58% by 24 months.
  • Children with the TLR4 Asp299Gly variant (22% of subjects) had a 4.91-fold increased risk of M. catarrhalis colonization at all three time points compared to wild-type.
  • Subjects with the TLR4 variant exhibited significantly higher nasopharyngeal bacterial loads of M. catarrhalis.

Conclusions:

  • The TLR4 Asp299Gly polymorphism is linked to an elevated risk of persistent M. catarrhalis colonization in children.
  • This genetic predisposition may impact the course of common childhood respiratory infections.

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