Type II alveolar cells play roles in macrophage-mediated host innate resistance to pulmonary mycobacterial infections by producing proinflammatory cytokines

Abstract

Roles of type II pneumocytes in macrophage (Mφ)-mediated host resistance to pulmonary Mycobacterium tuberculosis (MTB) and M. avium complex (MAC) infections were studied. Electron microscopy of the lung sections of mice given intratracheal infection indicated that the organisms invaded both Mφs and type II pneumocytes. When Mono-Mac-6 Mφs (MM6-Mφs) and A-549 type II pneumocytes (A-549 cells) were cocultivated, bacterial growth in MM6-Mφs was reduced by A-549 cell-derived soluble factors, indicating the roles of type II pneumocytes in Mφ-mediated host resistance to mycobacteria. MTB- or MAC-infected A-549 cells showed increased mitochondrial RNA expression of cytokines and surfactant proteins (SPs), in the order tumor necrosis factor-α (TNF-α) ≥ granulocyte-Mφ colony-stimulating factor (GM-CSF) > Mφ chemoattractant protein ≥ interleukin-8 > SP-D. Anti-TNF-α and anti-GM-CSF antibodies attenuated A-549 cell-dependent inhibition of intramacrophage mycobacteria, indicating their crucial roles in A-549 cell-mediated potentiation of Mφ antimycobacterial activity.