Extended Data Figure 2: Pathways for the clearance of bacteria and particles from the lower airways.

Inhaled agents such as bacteria (yellow) impact upon epithelium-lined surfaces in conducting airways or deposit in alveoli. Bacteria trapped in surface and glandular mucous secretions (green) are eliminated directly by MCC (1) or are killed and then eliminated by MCC (2). Bacteria that evade these mechanisms or deposit more deeply in the lungs are detected and phagocytosed by dendritic cells (DCs) and macrophages (3; present in the airways and alveoli, but shown only in the latter here for clarity). DCs and macrophages secrete IL-23 and facilitate innate anti-bacterial immune responses through innate myeloid- and lymphoid-cell (4), and monocyte and granulocyte recruitment (5). Recruited inflammatory cells accumulate in the lungs and kill bacteria through phagocytic, exocytic and extracellular trap-mediated mechanisms (6). To resolve inflammation, recruited leukocytes undergo apoptosis and are phagocytosed by macrophages, which then repress IL-23 production (7), undergo apoptosis (8) and are eliminated by MCC. In the studies presented here, we demonstrate that these defences are critically dependent upon the expression of Muc5b.