The interaction between mother and fetus and the development of allergic asthma

Abstract

The rising prevalence of asthma and atopic disease in industrialized countries in the last 50 years has raised important questions about how and why the disease develops in susceptible populations. Most asthma begins in childhood in association with allergic sensitization and the development of a TH2 phenotype. It is recognized that asthma arises in the context of a complex interaction between genetic factors and the evolving immune system of the infant and the environment to which it is exposed, which now includes its in utero exposure. Early life exposures that lead to allergen sensitization and airway damage, especially in the form of viral respiratory tract infections, may lead to disease induction that commence the process that leads in some to asthma. Asthma models and early life observations suggest that repeated exposure to allergens and viral infection perpetuate a state of chronic airway inflammation leading to a maladaptive innate immune response that fails to resolve, characterized by chronic airway inflammation, airway remodeling and airway hyperresponsiveness. This article will concentrate on the development of asthma in the context of early life and maternal influences, including the effect of asthma on both the fetus and the mother.

Keywords::

• airway epithelium
• allergy
• asthma
• dendritic cells
• innate immune response
• respiratory virus infection

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Multiple genetic factors and how they control airway innate immune activation in early life asthma.

• How the developing immune system becomes polarized to a TH2 response and whether this can be reversed.

• How epithelial innate immune activation becomes established and then fails to turn off in the context of asthma, especially the role of initiation and repair mechanisms and what influences these.

• How dendritic cell induction that promotes asthmatic responses from the epithelium and T lymphocytes becomes established and whether these signals can be reversed.

• How do impaired innate antiviral responses occur in asthmatic innate immune cells, is this controlled genetically/epigentically and how can this process be reversed.

• How does early life asthma development relate to the development of asthma in older subjects, both those with atopy but importantly also those in whom atopy does not appear to play a central role.

Notes