A new danger in the air: how pulmonary innate immunity copes with man-made airborne xenobiotics.

The pulmonary innate immune system has evolved over millions of years to provide swift detection of inhaled microbial agents and trigger well-balanced protective responses. Much more recent on the evolutionary scale is human activity, which has resulted in the release of a new class of potentially harmful, non-microbial compounds into the air. These xenobiotics include combustion by-products such as reactive oxygen species and polycyclic aromatic hydrocarbons. This review will summarize evidence showing how airborne xenobiotics can engage pulmonary innate immunity components at many levels. We will focus on potential effects of xenobiotics on airway dendritic cells, as these constitute key innate immune sensors in the lung, with the unique ability to initiate adaptive immunity. We propose that the aberrant processing of inhaled xenobiotics by an innate immune system that is now evolutionarily maladapted underlies the increase in chronic inflammatory lung diseases in modern times.

Between a cough and a wheeze: dendritic cells at the nexus of tobacco smoke-induced allergic airway sensitization.

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.