Innate immunity to inhaled particles: A new paradigm of collective recognition

Major progress has been achieved in recent years to elucidate mechanisms driving the early response of pulmonary innate immune cells to inhaled micrometric and nanometric particles. Mononuclear phagocytes promptly categorize particles, alert immune network and engage crescendo responses for particle clearance and homeostasis restoration. Negatively charged particles directly interact with scavenger receptors A and B (SR-A and SR-B) and consequently activate specific signaling pathways, resulting in the production of TNF and IL-1 family members, which coordinate effective innate immune responses. Cytokine secretion also arises after a simple contact between particle-associated radicals and cell membranes. Reactive particles engage the passive release of constitutive alarmins, ensuing particle- or TNF-α-induced cell death and membranolysis. Finally, the inflammasome machinery represents the decisive intracellular platform that finely tune immune pathways engaged after SR activation, alarmin release, TNF-α production and cell homeostasis perturbations. Disturbance of these collective recognition processes prolongs particle persistence and innate immune responses that generate long-lasting adaptive immunity and cause chronic lung diseases.