Microvesicles Derived from Human Bronchial Epithelial Cells Regulate Macrophage Activation During Mycobacterium abscessus Infection

Intercellular communication is important for host immunity
in response
to bacterial infections. Nontuberculous mycobacterium (NTM), such
as Mycobacterium abscessus (M. ab), is a group of environmental bacteria that
can cause severe lung infections in individuals with pre-existing
lung conditions, including cystic fibrosis (CF) and chronic obstructive
pulmonary disease (COPD). There is limited knowledge understanding
the interaction between airway epithelial cells and immune cells during
NTM infections. In this study, we characterized microvesicles (MVs)
released from uninfected and M. ab-infected
human bronchial epithelial cells and investigated the effect of these
MVs on the activation and polarization of THP-1-derived macrophages
in cell culture. Our results indicate that MVs released by M. ab-infected human bronchial epithelial cells stimulated
the activation of M2-polarized macrophages in cell culture when compared
to MVs released by uninfected cells. Additionally, the proteomic analysis
for isolated MVs showed that the proteins involved in the cell adhesion
pathway were enriched in MVs from M. ab-infected human bronchial epithelial cells compared to MVs from uninfected
cells. Among those, the cell surface protein, intercellular adhesion
molecule 1 (ICAM-1), regulated the uptake of MVs released by M. ab-infected human bronchial epithelial cells by
recipient macrophages in cell culture. In conclusion, our data suggest
that in response to M. ab infection,
human airway epithelial cells release MVs to modulate the activation
of macrophages, which are key cells for mycobacterial intracellular
survival in the host.