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Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection.
- Source :
-
Frontiers in immunology [Front Immunol] 2019 Mar 18; Vol. 10, pp. 458. Date of Electronic Publication: 2019 Mar 18 (Print Publication: 2019). - Publication Year :
- 2019
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Abstract
- Non-typeable Haemophilus influenzae (NTHi) causes persistent respiratory infections in patients with chronic obstructive pulmonary disease (COPD), probably linked to its capacity to invade and reside within pneumocytes. In the alveolar fluid, NTHi is in contact with pulmonary surfactant, a lipoprotein complex that protects the lung against alveolar collapse and constitutes the front line of defense against inhaled pathogens and toxins. Decreased levels of surfactant phospholipids have been reported in smokers and patients with COPD. The objective of this study was to investigate the effect of surfactant phospholipids on the host-pathogen interaction between NTHi and pneumocytes. For this purpose, we used two types of surfactant lipid vesicles present in the alveolar fluid: (i) multilamellar vesicles (MLVs, > 1 μm diameter), which constitute the tensioactive material of surfactant, and (ii) small unilamellar vesicles (SUVs, 0.1 μm diameter), which are generated after inspiration/expiration cycles, and are endocytosed by pneumocytes for their degradation and/or recycling. Results indicated that extracellular pulmonary surfactant binds to NTHi, preventing NTHi self-aggregation and inhibiting adhesion of NTHi to pneumocytes and, consequently, inhibiting NTHi invasion. In contrast, endocytosed surfactant lipids, mainly via the scavenger receptor SR-BI, did not affect NTHi adhesion but inhibited NTHi invasion by blocking bacterial uptake in pneumocytes. This blockade was made possible by inhibiting Akt phosphorylation and Rac1 GTPase activation, which are signaling pathways involved in NTHi internalization. Administration of the hydrophobic fraction of lung surfactant in vivo accelerated bacterial clearance in a mouse model of NTHi pulmonary infection, supporting the notion that the lipid component of lung surfactant protects against NTHi infection. These results suggest that alterations in surfactant lipid levels in COPD patients may increase susceptibility to infection by this pathogen.
- Subjects :
- Alveolar Epithelial Cells metabolism
Animals
Bacterial Adhesion drug effects
Endocytosis drug effects
Enzyme Activation drug effects
Extracellular Vesicles physiology
Haemophilus Infections immunology
Haemophilus influenzae isolation & purification
Haemophilus influenzae physiology
Host-Pathogen Interactions drug effects
Humans
Hydrophobic and Hydrophilic Interactions
Liposomes
Male
Mice
Neuropeptides antagonists & inhibitors
Otitis Media microbiology
Phosphorylation drug effects
Protein Processing, Post-Translational drug effects
Proto-Oncogene Proteins c-akt metabolism
Pulmonary Disease, Chronic Obstructive microbiology
Pulmonary Surfactants immunology
Rats
Rats, Sprague-Dawley
Receptors, Scavenger antagonists & inhibitors
Receptors, Scavenger physiology
Specific Pathogen-Free Organisms
rac1 GTP-Binding Protein antagonists & inhibitors
Alveolar Epithelial Cells drug effects
Haemophilus Infections prevention & control
Haemophilus influenzae drug effects
Pulmonary Surfactants pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30936871
- Full Text :
- https://doi.org/10.3389/fimmu.2019.00458