Alveolar Epithelial Cells Are Critical in Protection of the Respiratory Tract by Secretion of Factors Able To Modulate the Activity of Pulmonary Macrophages and Directly Control Bacterial Growth

Abstract

The respiratory epithelium is a physical and functional barrier actively involved in the clearance of environmental agents. The alveolar compartment is lined with membranous pneumocytes, known as type I alveolar epithelial cells (AEC I), and granular pneumocytes, type II alveolar epithelial cells (AEC II). AEC II are responsible for epithelial reparation upon injury and ion transport and are very active immunologically, contributing to lung defense by secreting antimicrobial factors. AEC II also secrete a broad variety of factors, such as cytokines and chemokines, involved in activation and differentiation of immune cells and are able to present antigen to specific T cells. Another cell type important in lung defense is the pulmonary macrophage (PuM). Considering the architecture of the alveoli, a good communication between the external and the internal compartments is crucial to mount effective responses. Our hypothesis is that being in the interface, AEC may play an important role in transmitting signals from the external to the internal compartment and in modulating the activity of PuM. For this, we collected supernatants from AEC unstimulated or stimulated in vitro with lipopolysaccharide (LPS). These AEC-conditioned media were used in various setups to test for the effects on a number of macrophage functions: (i) migration, (ii) phagocytosis and intracellular control of bacterial growth, and (iii) phenotypic changes and morphology. Finally, we tested the direct effect of AEC-conditioned media on bacterial growth. We found that AEC-secreted factors had a dual effect, on one hand controlling bacterial growth and on the other hand increasing macrophage activity.

The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection

“…It is also possible that certain specific mediators produced exclusively by macrophages and not by the epithelial cells contribute to the difference in their ability to mediate immune clearance of A. baumannii. Cell type-specific differences between pulmonary macrophages and epithelial cells in their production of immune mediators to mycobacterium infection have been reported before (37,38).…”

d-Amino acids incorporation in the frog skin-derived peptide esculentin-1a(1-21)NH2 is beneficial for its multiple functions

“…Taking into account that type II pulmonary epithelial cells are responsible for epithelial reparation upon injury (Chuquimia et al 2013), we studied the peptides' capability to promote migration of A549 cells in an in vitro pseudo-"wound" healing assay, by means of special cell-culture inserts. Both peptides were able to stimulate the closure of a gap produced in a monolayer of A549 cells.…”

Infection of A549 human type II epithelial cells with Mycobacterium tuberculosis induces changes in mitochondrial morphology, distribution and mass that are dependent on the early secreted antigen, ESAT-6

“…Composed of type I and II pneumocytes, this cell layer provides a barrier function which involves detection of pathogens through pattern recognition receptors, as well as secretion of surfactant proteins, cytokines, chemotactic factors, and antimicrobial molecules [4,5]. Although alveolar macrophages and other professional phagocytic immune cells such as dendritic cells, monocytes and neutrophils have been the focus of the majority of studies investigating the process of Mtb infection, increasing evidence implicates the alveolar epithelium and in particular type II pneumocytes in both host cell defense and bacterial pathogenicity [6].…”