Immunomodulatory role for membrane vesicles released by THP-1 macrophages and respiratory pathogens during macrophage infection

Abstract

BackgroundDuring infection, inflammation is partially driven by the release of mediators which facilitate intercellular communication. Amongst these mediators are small membrane vesicles (MVs) that can be released by both host cells and Gram-negative and -positive bacteria. Bacterial membrane vesicles are known to exert immuno-modulatory and -stimulatory actions. Moreover, it has been proposed that host cell-derived vesicles, released during infection, also have immunostimulatory properties. In this study, we assessed the release and activity of host cell-derived and bacterial MVs during the first hours following infection of THP-1 macrophages with the common respiratory pathogens non-typeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa.ResultsUsing a combination of flow cytometry, tunable resistive pulse sensing (TRPS)-based analysis and electron microscopy, we demonstrated that the release of MVs occurs by both host cells and bacteria during infection. MVs released during infection and bacterial culture were found to induce a strong pro-inflammatory response by naive THP-1 macrophages. Yet, these MVs were also found to induce tolerance of host cells to secondary immunogenic stimuli and to enhance bacterial adherence and the number of intracellular bacteria.ConclusionsBacterial MVs may play a dual role during infection, as they can both trigger and dampen immune responses thereby contributing to immune defence and bacterial survival.

Dual and Triple Epithelial Coculture Model Systems with Donor-Derived Microbiota and THP-1 Macrophages To Mimic Host-Microbe Interactions in the Human Sinonasal Cavities

“…Next to this, (alternatively activated) macrophage infiltration in (polyp) tissue in chronic rhinosinusitis with nasal polyps could play a role in disease perpetuation (30)(31)(32)34). Through the enforcement of an inflammatory response or the induction of a more immunotolerant environment upon repeated exposure (35,77,78), the tissue macrophages can, directly and indirectly through the epithelium, shape the microbial community by preventing the outgrowth of particular bacteria. This relationship is bidirectional, since the resident microbiota and its metabolites will induce (anti-)inflammatory responses in the human host.…”

Host-microbe cross-talk in the lung microenvironment: implications for understanding and treating chronic lung disease

“…Besides supporting the survival of the parent bacteria, OMVs may also play role in the progression of pulmonary diseases. Bacteria frequently associated with COPD exacerbations are known to release OMVs [148]. Furthermore, macrophages stimulated with OMVs derived from prominent airway pathogens such as P. aeruginosa, H. influenzae or M. catarrhalis release higher amounts of tumour necrosis factor-α and IL-6 [148].…”

“…Bacteria frequently associated with COPD exacerbations are known to release OMVs [ 148 ]. Furthermore, macrophages stimulated with OMVs derived from prominent airway pathogens such as P. aeruginosa , H. influenzae or M. catarrhalis release higher amounts of tumour necrosis factor-α and IL-6 [ 148 ]. Legionella -derived OMVs significantly enhanced bacterial replication in macrophages [ 149 ], and bacteria-free P. aeruginosa OMVs have been shown to potently induce pulmonary inflammation in mice [ 150 ], strengthening the idea that OMVs exert disease-promoting activities.…”

Alveolar macrophage‐derived extracellular vesicles inhibit endosomal fusion of influenza virus

“…Human THP‐1 monocytes (ATCC TIB‐202) were maintained in 10% FBS‐supplemented RPMI. For THP‐1 differentiation into macrophages (Volgers et al , ), cells were stimulated for 72 h with 100 nM phorbol 12‐myristate 13‐acetate (Sigma). Cell lines were used between passages 5 and 40.…”