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

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.”