Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection
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.
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Format: | artículo biblioteca |
Language: | English |
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Frontiers Media
2019-03-18
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Subjects: | Nontypeable Haemophilus influenzae, Pulmonary surfactant, Phospholipids, Alveolar epithelial cells, Host-pathogen interaction,, Bacterial invasion, RAC-1, PI3K/Akt, |
Online Access: | http://hdl.handle.net/10261/191782 http://dx.doi.org/10.13039/501100002911 |
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dig-idab-es-10261-1917822021-12-28T16:10:04Z Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection García-Fojeda, Belén González-Carnicero, Zoe Lorenzo, Alba de Minutti, Carlos M. Tapia, Lidia de Euba, Begoña Iglesias-Ceacero, Alba Castillo-Lluva, Sonia Garmendia, Juncal Casals, Cristina Universidad Complutense de Madrid Nontypeable Haemophilus influenzae Pulmonary surfactant Phospholipids Alveolar epithelial cells Host-pathogen interaction, Bacterial invasion RAC-1 PI3K/Akt 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. We thank the animal facility of the Faculty of Biology and Confocal Microscopy Unit of Universidad Complutense de Madrid for excellent technical support. We acknowledge Dr. O. Cañadas’s help in dynamic light scattering and zeta potential measurements, and Dr. I. Rodríguez-Arce’s help with animal experiments. Peer reviewed 2019-09-27T11:41:00Z 2019-09-27T11:41:00Z 2019-03-18 artículo http://purl.org/coar/resource_type/c_6501 Frontiers in Immunology 10: 458 (2019) 1664-3224 http://hdl.handle.net/10261/191782 10.3389/fimmu.2019.00458 http://dx.doi.org/10.13039/501100002911 30936871 en Publisher's version https://doi.org/10.3389/fimmu.2019.00458 Sí open Frontiers Media |
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Nontypeable Haemophilus influenzae Pulmonary surfactant Phospholipids Alveolar epithelial cells Host-pathogen interaction, Bacterial invasion RAC-1 PI3K/Akt Nontypeable Haemophilus influenzae Pulmonary surfactant Phospholipids Alveolar epithelial cells Host-pathogen interaction, Bacterial invasion RAC-1 PI3K/Akt |
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Nontypeable Haemophilus influenzae Pulmonary surfactant Phospholipids Alveolar epithelial cells Host-pathogen interaction, Bacterial invasion RAC-1 PI3K/Akt Nontypeable Haemophilus influenzae Pulmonary surfactant Phospholipids Alveolar epithelial cells Host-pathogen interaction, Bacterial invasion RAC-1 PI3K/Akt García-Fojeda, Belén González-Carnicero, Zoe Lorenzo, Alba de Minutti, Carlos M. Tapia, Lidia de Euba, Begoña Iglesias-Ceacero, Alba Castillo-Lluva, Sonia Garmendia, Juncal Casals, Cristina Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection |
description |
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. |
author2 |
Universidad Complutense de Madrid |
author_facet |
Universidad Complutense de Madrid García-Fojeda, Belén González-Carnicero, Zoe Lorenzo, Alba de Minutti, Carlos M. Tapia, Lidia de Euba, Begoña Iglesias-Ceacero, Alba Castillo-Lluva, Sonia Garmendia, Juncal Casals, Cristina |
format |
artículo |
topic_facet |
Nontypeable Haemophilus influenzae Pulmonary surfactant Phospholipids Alveolar epithelial cells Host-pathogen interaction, Bacterial invasion RAC-1 PI3K/Akt |
author |
García-Fojeda, Belén González-Carnicero, Zoe Lorenzo, Alba de Minutti, Carlos M. Tapia, Lidia de Euba, Begoña Iglesias-Ceacero, Alba Castillo-Lluva, Sonia Garmendia, Juncal Casals, Cristina |
author_sort |
García-Fojeda, Belén |
title |
Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection |
title_short |
Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection |
title_full |
Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection |
title_fullStr |
Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection |
title_full_unstemmed |
Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection |
title_sort |
lung surfactant lipids provide immune protection against haemophilus influenzae respiratory infection |
publisher |
Frontiers Media |
publishDate |
2019-03-18 |
url |
http://hdl.handle.net/10261/191782 http://dx.doi.org/10.13039/501100002911 |
work_keys_str_mv |
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