Allergens and Respiratory Pollutants: The Role of Innate Immunity

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An introduction to allergic inflammation and the innate immune sensing of dangerous ambient pollutants by the dendritic cell

Marc A. Williams

Abstract

Hematopoiesis is a process of cellular development and differentiation that, in adults at least, originates in the bone marrow and in the case of the myeloid cellular system continues in the peripheral blood and many of the organs to which such cells migrate. Through a series of differentiation pathways, subsets of myeloid cells are generated. Among them are professional antigen-presenting cells, termed dendritic cells or DC, that are derived from a common myeloid progenitor and constitute the most important specialized cell of the innate immune system. In the airway, DC are ideally located to rapidly sense and respond to exogenous triggers of pulmonary inflammation including such diverse environmental stimuli as aeroallergens, respirable particulate pollutants or other xenobiotics. Though the airway wall is a biologically complex cellular barrier and provides a major component of the innate immune system, interdigitated throughout the bronchial epithelium and parenchyma are several DC subsets that collectively sense and respond not only to infectious microorganisms that traffic to the lung, but also respirable environmental pollutant particles. Thus communication between the pulmonary epithelia and the interdigitating DC contributes to the maintenance of the lung as an immune-privileged organ. However, exposure of the lung to environmental airborne pollutant particles may provoke allergic inflammation. Moreover, airway inflammation in allergic asthma reflects an aberrant immune response against otherwise harmless inhaled allergens. The association between particulate air pollution and allergic asthma has been identified by epidemiological evidence, yet the biological effects of particulate air pollution in host immunity remain poorly studied. Given the escalating global burden of an increasingly prevalent and complex mixture of ambient airborne pollutants, it is no surprise that such anthropogenic triggers of allergic immune responsiveness are contributing to a variety of disease states, including allergic asthma and cardiovascular disease, enhanced susceptibility to pulmonary viral or bacterial infections and exacerbations of pre-existing airway diseases like chronic obstructive pulmonary disease (COPD). In this chapter, an overview of innate and adaptive immunology is provided that places in context the important role that the host innate immune system plays in sensing and responding to exogenous danger signals such as respirable particulate pollutants as well as an overview of some of the mechanisms that may be responsible for activating the innate allergic responses of DC. Collectively, respirable ambient pollutant particles can be considered danger signals of immune reactivity and the activated allergic inflammatory response sensed by dendritic cells as the enemy within.

Keywords

innate immunity

dendritic cell

inflammation

asthma

Hygiene Hypothesis

toll-like receptor

pollution

airborne particulate matter

immunotoxicology

1.1 Introduction

In scientific research, particularly in the life sciences, history tells us that the only thing we are certain of is being certain of nothing at all, hence the importance of hypothesis-driven research. At the Battle of Waterloo of 1815, the Duke of Wellington famously stated after defeating the French armies of Napoleon: All the business of war, and indeed all the business of life, is to endeavour to find out what you don’t know by what you do; that’s what I call ‘guessing what was at the other side of the hill.’ In other words, one can consider this quote in the context of delineating the relative roles of the dendritic cell in allergic immunity and inflammation by hypothesis-driven research and experimentation. There have been several seminal works, including work of our own, (¹–¹³) that have hypothesized an important role for the dendritic cell in driving allergic immune responses and contributing to the health effects associated with trafficking of respirable ambient pollutants to the lower airways.

Ambient air pollution, including coarse, fine and ultrafine particulate matter, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, mercury, semi-volatile organic pollutants and a host of others emitted into the atmospheric air that we breathe presents serious challenges to human health. Sources of ambient airborne pollutants include diesel engine vehicles and trucks, shipping, aircraft, light and heavy industrial smoke-stacks, wood -and fossil-burning heating and cooking stoves, wild-fires, pesticides from agricultural sources, coal-burning power-plants and many other small fossil-fuel powered devices or machines. Sophisticated atmospheric and climatological research has shown that airborne pollutants in the lower atmosphere can be propelled to higher altitudes which are then shifted to geographically distant sites far from the source of the emitted pollutants by prevailing winds and other meteorological influences. This means of course that airborne pollutants can breach state lines in the continental US, traverse oceans and seas and even cross entire continents.

Moreover, the realization that the problem of geographically migratory ambient airborne pollutants and the issue of degrading air quality may worsen in the decades ahead is a cause for concern. This is particularly relevant when one considers the improving standards of living in developing countries, and thus enhanced demands for power and public transportation and with it escalating anthropogenic emissions associated with increased demands for transport and industry. As important as these considerations are, they will not be a major focus of this chapter and the reader is guided towards several publically available documents published by the US Environmental Protection Agency, the National Research Council, the National Oceanic and Atmospheric Administration, The National Aeronautics and Space Administration, and the National Science