Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses

ABSTRACT Gram-positive bacteria, including the major respiratory pathogen Streptococcus pneumoniae, were recently shown to produce extracellular vesicles (EVs) that likely originate from the plasma membrane and are released into the extracellular environment. EVs may function as cargo for many bacte...

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Autores principales:	Mario Codemo, Sandra Muschiol, Federico Iovino, Priyanka Nannapaneni, Laura Plant, Sun Nyunt Wai, Birgitta Henriques-Normark
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Streptococcus pneumoniae cellular and humoral defense complement extracellular vesicles pneumococcal evasion of immune response pneumococci Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d7617127b82645339f7752e9eef578f8
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spelling	oai:doaj.org-article:d7617127b82645339f7752e9eef578f82021-11-15T15:53:26ZImmunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses10.1128/mBio.00559-182150-7511https://doaj.org/article/d7617127b82645339f7752e9eef578f82018-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00559-18https://doaj.org/toc/2150-7511ABSTRACT Gram-positive bacteria, including the major respiratory pathogen Streptococcus pneumoniae, were recently shown to produce extracellular vesicles (EVs) that likely originate from the plasma membrane and are released into the extracellular environment. EVs may function as cargo for many bacterial proteins, however, their involvement in cellular processes and their interactions with the innate immune system are poorly understood. Here, EVs from pneumococci were characterized and their immunomodulatory effects investigated. Pneumococcal EVs were protruding from the bacterial surface and released into the medium as 25 to 250 nm lipid stained vesicles containing a large number of cytosolic, membrane, and surface-associated proteins. The cytosolic pore-forming toxin pneumolysin was significantly enriched in EVs compared to a total bacterial lysate but was not required for EV formation. Pneumococcal EVs were internalized into A549 lung epithelial cells and human monocyte-derived dendritic cells and induced proinflammatory cytokine responses irrespective of pneumolysin content. EVs from encapsulated pneumococci were recognized by serum proteins, resulting in C3b deposition and formation of C5b-9 membrane attack complexes as well as factor H recruitment, depending on the presence of the choline binding protein PspC. Addition of EVs to human serum decreased opsonophagocytic killing of encapsulated pneumococci. Our data suggest that EVs may act in an immunomodulatory manner by allowing delivery of vesicle-associated proteins and other macromolecules into host cells. In addition, EVs expose targets for complement factors in serum, promoting pneumococcal evasion of humoral host defense. IMPORTANCE Streptococcus pneumoniae is a major contributor to morbidity and mortality worldwide, being the major cause of milder respiratory tract infections such as otitis and sinusitis and of severe infections such as community-acquired pneumonia, with or without septicemia, and meningitis. More knowledge is needed on how pneumococci interact with the host, deliver virulence factors, and activate immune defenses. Here we show that pneumococci form extracellular vesicles that emanate from the plasma membrane and contain virulence properties, including enrichment of pneumolysin. We found that pneumococcal vesicles can be internalized into epithelial and dendritic cells and bind complement proteins, thereby promoting pneumococcal evasion of complement-mediated opsonophagocytosis. They also induce pneumolysin-independent proinflammatory responses. We suggest that these vesicles can function as a mechanism for delivery of pneumococcal proteins and other immunomodulatory components into host cells and help pneumococci to avoid complement deposition and phagocytosis-mediated killing, thereby possibly contributing to the symptoms found in pneumococcal infections.Mario CodemoSandra MuschiolFederico IovinoPriyanka NannapaneniLaura PlantSun Nyunt WaiBirgitta Henriques-NormarkAmerican Society for MicrobiologyarticleStreptococcus pneumoniaecellular and humoral defensecomplementextracellular vesiclespneumococcal evasion of immune responsepneumococciMicrobiologyQR1-502ENmBio, Vol 9, Iss 2 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pneumoniae cellular and humoral defense complement extracellular vesicles pneumococcal evasion of immune response pneumococci Microbiology QR1-502
spellingShingle	Streptococcus pneumoniae cellular and humoral defense complement extracellular vesicles pneumococcal evasion of immune response pneumococci Microbiology QR1-502 Mario Codemo Sandra Muschiol Federico Iovino Priyanka Nannapaneni Laura Plant Sun Nyunt Wai Birgitta Henriques-Normark Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses
description	ABSTRACT Gram-positive bacteria, including the major respiratory pathogen Streptococcus pneumoniae, were recently shown to produce extracellular vesicles (EVs) that likely originate from the plasma membrane and are released into the extracellular environment. EVs may function as cargo for many bacterial proteins, however, their involvement in cellular processes and their interactions with the innate immune system are poorly understood. Here, EVs from pneumococci were characterized and their immunomodulatory effects investigated. Pneumococcal EVs were protruding from the bacterial surface and released into the medium as 25 to 250 nm lipid stained vesicles containing a large number of cytosolic, membrane, and surface-associated proteins. The cytosolic pore-forming toxin pneumolysin was significantly enriched in EVs compared to a total bacterial lysate but was not required for EV formation. Pneumococcal EVs were internalized into A549 lung epithelial cells and human monocyte-derived dendritic cells and induced proinflammatory cytokine responses irrespective of pneumolysin content. EVs from encapsulated pneumococci were recognized by serum proteins, resulting in C3b deposition and formation of C5b-9 membrane attack complexes as well as factor H recruitment, depending on the presence of the choline binding protein PspC. Addition of EVs to human serum decreased opsonophagocytic killing of encapsulated pneumococci. Our data suggest that EVs may act in an immunomodulatory manner by allowing delivery of vesicle-associated proteins and other macromolecules into host cells. In addition, EVs expose targets for complement factors in serum, promoting pneumococcal evasion of humoral host defense. IMPORTANCE Streptococcus pneumoniae is a major contributor to morbidity and mortality worldwide, being the major cause of milder respiratory tract infections such as otitis and sinusitis and of severe infections such as community-acquired pneumonia, with or without septicemia, and meningitis. More knowledge is needed on how pneumococci interact with the host, deliver virulence factors, and activate immune defenses. Here we show that pneumococci form extracellular vesicles that emanate from the plasma membrane and contain virulence properties, including enrichment of pneumolysin. We found that pneumococcal vesicles can be internalized into epithelial and dendritic cells and bind complement proteins, thereby promoting pneumococcal evasion of complement-mediated opsonophagocytosis. They also induce pneumolysin-independent proinflammatory responses. We suggest that these vesicles can function as a mechanism for delivery of pneumococcal proteins and other immunomodulatory components into host cells and help pneumococci to avoid complement deposition and phagocytosis-mediated killing, thereby possibly contributing to the symptoms found in pneumococcal infections.
format	article
author	Mario Codemo Sandra Muschiol Federico Iovino Priyanka Nannapaneni Laura Plant Sun Nyunt Wai Birgitta Henriques-Normark
author_facet	Mario Codemo Sandra Muschiol Federico Iovino Priyanka Nannapaneni Laura Plant Sun Nyunt Wai Birgitta Henriques-Normark
author_sort	Mario Codemo
title	Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses
title_short	Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses
title_full	Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses
title_fullStr	Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses
title_full_unstemmed	Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses
title_sort	immunomodulatory effects of pneumococcal extracellular vesicles on cellular and humoral host defenses
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/d7617127b82645339f7752e9eef578f8
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Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses

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