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 (Mphi)-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 Mphis and type II pneumocytes. When Mono-Mac-6 Mphis(MM6-Mphis) and A-549 type II pneumocytes (A-549 cells) were cocultivated, bacterial growth in MM6-Mphis was reduced by A-549 cell-derived soluble factors, indicating the roles of type II pneumocytes in Mphi-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-alpha (TNF-alpha) > or = granulocyte-Mphi colony-stimulating factor (GM-CSF) > Mphi chemoattractant protein > or = interleukin-8 > SP-D. Anti-TNF-alpha 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 Mphi antimycobacterial activity.

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4

“…Also, growth of mycobacteria in MM6 cells was reduced when MM6 were in coculture with A549 cells, which was attributed to A549-derived cytokines (particularly TNF) (60). Our results on transcellular conversion of LTC 4 to LTD 4 are in line with an increased inflammatory response due to cell interactions and to interactions between myeloid cells and epithelium-derived exosomes.…”

Role of Primary Human Alveolar Epithelial Cells in Host Defense against Francisella tularensis Infection

“…ATII cells differentiate into ATI cells in 5 to 8 days. It is easy to discern ATI from ATII cells, as ATI cells are large flat cells (30,46). Primary HPMEC (Clonetics Cell Systems-Cambrex, Walkerville, Inc.) were grown and maintained in microvascular endothelial cell medium 2 (Clonetics) enhanced with the Bullet kit supplements provided by the manufacturer (Clonetics).…”

Dispensability of Surfactant Proteins A and D in Immune Control ofMycobacterium tuberculosisInfection following Aerosol Challenge of Mice

“…Nevertheless, despite the pulmonary defects of SP-D-deficient mice (6,42,47) and the presence of foamy macrophages (2, 47), we show that such activities are dispensable in a murine aerosol challenge model of TB. This may be because alveolar macrophages are an early and transient host for the bacteria, which quickly establish infection in monocyte-derived cells recruited from the blood (34,40) and show no differences in our experiments.…”