Abstract

Exposure to cigarette smoke represents a major risk factor for the development of asthma. Enhanced sensitization toward allergens has been observed in humans and laboratory animals exposed to cigarette smoke. Pulmonary dendritic cells (DCs) are crucially involved in sensitization toward allergens and play an important role in the development of T helper (Th)2-mediated allergic airway inflammation. We propose the concept that aberrant DC activation forms the basis for the deviation of the lung's default tolerogenic response toward allergic inflammation when harmless antigens are concomittantly inhaled with tobacco smoke. This review will summarize evidence suggesting that tobacco smoke can achieve this effect by providing numerous triggers of innate immunity, which can profoundly modulate airway DC biology. Tobacco smoke can affect the airway DC network either directly or indirectly by causing the release of DC-targeted mediators from the pulmonary tissue environment, resulting in the induction of a Th2-oriented pathological immune response. A thorough knowledge of the molecular pathways involved may open the door to novel approaches in the treatment of asthma.