Drivers of persistent infection: pathogen-induced extracellular vesicles

2018 ◽  
Vol 62 (2) ◽  
pp. 135-147 ◽  
Author(s):  
Michael J. Cipriano ◽  
Stephen L. Hajduk
Keyword(s):  
Immune Responses ◽  
Extracellular Vesicles ◽  
Host Cells ◽  
Infected Host ◽  
Immune Recognition ◽  
Adhesive Properties ◽  
Host Immune Responses ◽  
Recognition And Response ◽  
And Function ◽  
Induced Changes

Extracellular vesicles (EVs) are produced by invading pathogens and also by host cells in response to infection. The origin, composition, and function of EVs made during infection are diverse and provide effective vehicles for localized and broad dissimilation of effector molecules in the infected host. Extracellular pathogens use EVs to communicate with each other by sensing the host environment contributing to social motility, tissue tropism, and persistence of infection. Pathogen-derived EVs can also interact with host cells to influence the adhesive properties of host membranes and to alter immune recognition and response. Intracellular pathogens can affect both the protein and RNA content of EVs produced by infected host cells. Release of pathogen-induced host EVs can affect host immune responses to infection. In this review, we will describe both the biogenesis and content of EVs produced by a number of diverse pathogens. In addition, we will examine the pathogen-induced changes to EVs produced by infected host cells.

scholarly journals Extracellular Vesicles from Different Pneumococcal Serotypes Are Internalized by Macrophages and Induce Host Immune Responses

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1530
Author(s):  
Alfonso Olaya-Abril ◽  
Rafael Prados-Rosales ◽  
José A. González-Reyes ◽  
Arturo Casadevall ◽  
Liise-anne Pirofski ◽  
...  
Keyword(s):  
Immune Response ◽  
Biological Activity ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
Host Cells ◽  
Pneumococcal Serotypes ◽  
Human Pathogen ◽  
Host Immune Responses ◽  
Serotype 1 ◽  
Transient Loss

Bacterial extracellular vesicles are membranous ultrastructures released from the cell surface. They play important roles in the interaction between the host and the bacteria. In this work, we show how extracellular vesicles produced by four different serotypes of the important human pathogen, Streptococcus pneumoniae, are internalized by murine J774A.1 macrophages via fusion with the membrane of the host cells. We also evaluated the capacity of pneumococcal extracellular vesicles to elicit an immune response by macrophages. Macrophages treated with the vesicles underwent a serotype-dependent transient loss of viability, which was further reverted. The vesicles induced the production of proinflammatory cytokines, which was higher for serotype 1 and serotype 8-derived vesicles. These results demonstrate the biological activity of extracellular vesicles of clinically important pneumococcal serotypes.

scholarly journals Glycopeptides and -Mimetics to Detect, Monitor and Inhibit Bacterial and Viral Infections: Recent Advances and Perspectives

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1004 ◽  
Author(s):  
Sandra Behren ◽  
Ulrika Westerlind
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Viral Infections ◽  
Host Cells ◽  
Initial Contact ◽  
Host Immune Responses ◽  
Recent Advances ◽  
Multivalent Display ◽  
Important Objective ◽  
Pathogenic Infection

The initial contact of pathogens with host cells is usually mediated by their adhesion to glycan structures present on the cell surface in order to enable infection. Furthermore, glycans play important roles in the modulation of the host immune responses to infection. Understanding the carbohydrate-pathogen interactions are of importance for the development of novel and efficient strategies to either prevent, or interfere with pathogenic infection. Synthetic glycopeptides and mimetics thereof are capable of imitating the multivalent display of carbohydrates at the cell surface, which have become an important objective of research over the last decade. Glycopeptide based constructs may function as vaccines or anti-adhesive agents that interfere with the ability of pathogens to adhere to the host cell glycans and thus possess the potential to improve or replace treatments that suffer from resistance. Additionally, synthetic glycopeptides are used as tools for epitope mapping of antibodies directed against structures present on various pathogens and have become important to improve serodiagnostic methods and to develop novel epitope-based vaccines. This review will provide an overview of the most recent advances in the synthesis and application of glycopeptides and glycopeptide mimetics exhibiting a peptide-like backbone in glycobiology.

scholarly journals Production of Eicosanoids and Other Oxylipins by Pathogenic Eukaryotic Microbes

2003 ◽  
Vol 16 (3) ◽  
pp. 517-533 ◽  
Author(s):  
Mairi C. Noverr ◽  
John R. Erb-Downward ◽  
Gary B. Huffnagle
Keyword(s):  
Immune Responses ◽  
Pathogenic Fungi ◽  
Host Cells ◽  
Chemokine Production ◽  
Host Immune Responses ◽  
Potential Link ◽  
Leukocyte Chemotaxis ◽  
Eukaryotic Microbes ◽  
Precise Role

SUMMARY Oxylipins are oxygenated metabolites of fatty acids. Eicosanoids are a subset of oxylipins and include the prostaglandins and leukotrienes, which are potent regulators of host immune responses. Host cells are one source of eicosanoids and oxylipins during infection; however, another potential source of eicosanoids is the pathogen itself. A broad range of pathogenic fungi, protozoa, and helminths produce eicosanoids and other oxylipins by novel synthesis pathways. Why do these organisms produce oxylipins? Accumulating data suggest that phase change and differentiation in these organisms are controlled by oxylipins, including prostaglandins and lipoxygenase products. The precise role of pathogen-derived eicosanoids in pathogenesis remains to be determined, but the potential link between pathogen eicosanoids and the development of TH2 responses in the host is intriguing. Mammalian prostaglandins and leukotrienes have been studied extensively, and these molecules can modulate Th1 versus Th2 immune responses, chemokine production, phagocytosis, lymphocyte proliferation, and leukocyte chemotaxis. Thus, eicosanoids and oxylipins (host or microbe) may be mediators of a direct host-pathogen “cross-talk” that promotes chronic infection and hypersensitivity disease, common features of infection by eukaryotic pathogens.

scholarly journals Transcriptome Analysis of Mouse Brain Infected with Toxoplasma gondii

2013 ◽  
Vol 81 (10) ◽  
pp. 3609-3619 ◽  
Author(s):  
Sachi Tanaka ◽  
Maki Nishimura ◽  
Fumiaki Ihara ◽  
Junya Yamagishi ◽  
Yutaka Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Mouse Brain ◽  
Transcriptome Analysis ◽  
Host Cells ◽  
Content Type ◽  
Host Immune Responses ◽  
Wide Range ◽  
The Brain

ABSTRACTToxoplasma gondiiis an obligate intracellular parasite that invades a wide range of vertebrate host cells. Chronic infections withT. gondiibecome established in the tissues of the central nervous system, where the parasites may directly or indirectly modulate neuronal function. However, the mechanisms underlying parasite-induced neuronal disorder in the brain remain unclear. This study evaluated host gene expression in mouse brain following infection withT. gondii. BALB/c mice were infected with the PLK strain, and after 32 days of infection, histopathological lesions in the frontal lobe were found to be more severe than in other areas of the brain. Total RNA extracted from infected and uninfected mouse brain samples was subjected to transcriptome analysis using RNA sequencing (RNA-seq). In theT. gondii-infected mice, 935 mouse brain genes were upregulated, whereas 12 genes were downregulated. GOstat analysis predicted that the upregulated genes were primarily involved in host immune responses and cell activation. Positive correlations were found between the numbers of parasites in the infected mouse brains and the expression levels of genes involved in host immune responses. In contrast, genes that had a negative correlation with parasite numbers were predicted to be involved in neurological functions, such as small-GTPase-mediated signal transduction and vesicle-mediated transport. Furthermore, differential gene expression was observed between mice exhibiting the clinical signs of toxoplasmosis and those that did not. Our findings may provide insights into the mechanisms underlying neurological changes duringT. gondiiinfection.

scholarly journals Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

2016 ◽  
Vol 90 (8) ◽  
pp. 3810-3818 ◽  
Author(s):  
Bjoern Meyer ◽  
Hinh Ly
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Multiorgan Failure ◽  
Hemorrhagic Fever ◽  
Innate Immune ◽  
Lassa Virus ◽  
Immune Recognition ◽  
African Countries ◽  
Host Immune Responses

Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.

scholarly journals CD4+ T Cells and Toll-Like Receptors Recognize Salmonella Antigens Expressed in Bacterial Surface Organelles

2005 ◽  
Vol 73 (3) ◽  
pp. 1350-1356 ◽  
Author(s):  
Molly A. Bergman ◽  
Lisa A. Cummings ◽  
Sara L. Rassoulian Barrett ◽  
Kelly D. Smith ◽  
J. Cano Lara ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Membrane Vesicles ◽  
Surface Modifications ◽  
Immune Recognition ◽  
Toll Like Receptors ◽  
Bacterial Surface ◽  
Host Immune Responses ◽  
Adaptive Immune ◽  
Host Tissues

ABSTRACT A better understanding of immunity to infection is revealed from the characteristics of microbial ligands recognized by host immune responses. Murine infection with the intracellular bacterium Salmonella generates CD4+ T cells that specifically recognize Salmonella proteins expressed in bacterial surface organelles such as flagella and membrane vesicles. These natural Salmonella antigens are also ligands for Toll-like receptors (TLRs) or avidly associated with TLR ligands such as lipopolysaccharide (LPS). PhoP/PhoQ, a regulon controlling Salmonella virulence and remodeling of LPS to resist innate immunity, coordinately represses production of surface-exposed antigens recognized by CD4+ T cells and TLRs. These data suggest that genetically coordinated surface modifications may provide a growth advantage for Salmonella in host tissues by limiting both innate and adaptive immune recognition.

scholarly journals Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyan clinical isolate defines a core parasite secretome

2017 ◽  
Vol 2 ◽  
pp. 50 ◽  
Author(s):  
Abdirahman Abdi ◽  
Lu Yu ◽  
David Goulding ◽  
Martin K. Rono ◽  
Philip Bejon ◽  
...  
Keyword(s):  
Clinical Isolate ◽  
Extracellular Vesicles ◽  
Genetic Material ◽  
Host Cells ◽  
Mass Spectrometry Data ◽  
Host Interactions ◽  
Effector Molecules ◽  
Host Immune Responses ◽  
Maurer's Clefts

Background: Many pathogens secrete effector molecules to subvert host immune responses, to acquire nutrients, and/or to prepare host cells for invasion. One of the ways that effector molecules are secreted is through extracellular vesicles (EVs) such as exosomes. Recently, the malaria parasite P. falciparum has been shown to produce EVs that can mediate transfer of genetic material between parasites and induce sexual commitment. Characterizing the content of these vesicles may improve our understanding of P. falciparum pathogenesis and virulence. Methods: Previous studies of P. falciparum EVs have been limited to long-term adapted laboratory isolates. In this study, we isolated EVs from a Kenyan P. falciparum clinical isolate that had been adapted to in vitro culture for a relatively shorter period, and characterized their protein content by mass spectrometry (data are available via ProteomeXchange, with identifier PXD006925). Results: We show that P. falciparum extracellular vesicles (PfEVs) are enriched in proteins found within the exomembrane compartments of infected erythrocytes such as Maurer’s clefts (MCs), as well as the secretory endomembrane compartments in the apical end of the merozoites, suggesting that PfEVs may play a role in parasite-host interactions. Comparison of this dataset with previously published datasets helps to define a core secretome present in PfEVs. Conclusions: P. falciparum extracellular vesicles contain virulence-associated parasite proteins. Analysis of PfEVs contents from a range of clinical isolates, and their functional validation may improve our understanding of the virulence mechanisms of the parasite, and potentially identify new targets for interventions or diagnostics.

scholarly journals The Crossroads of Glycoscience, Infection, and Immunology

2021 ◽  
Vol 12 ◽  
Author(s):  
Tanya R. McKitrick ◽  
Margaret E. Ackerman ◽  
Robert M. Anthony ◽  
Clay S. Bennett ◽  
Michael Demetriou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Host Response ◽  
Immune Cell ◽  
Microbial Infection ◽  
Surface Receptors ◽  
Host Interactions ◽  
Host Immune Responses ◽  
Immune Mediators ◽  
Immune Mediated ◽  
And Function

Advances in experimental capabilities in the glycosciences offer expanding opportunities for discovery in the broad areas of immunology and microbiology. These two disciplines overlap when microbial infection stimulates host immune responses and glycan structures are central in the processes that occur during all such encounters. Microbial glycans mediate host-pathogen interactions by acting as surface receptors or ligands, functioning as virulence factors, impeding host immune responses, or playing other roles in the struggle between host and microbe. In the context of the host, glycosylation drives cell–cell interactions that initiate and regulate the host response and modulates the effects of antibodies and soluble immune mediators. This perspective reports on a workshop organized jointly by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research in May 2020. The conference addressed the use of emerging glycoscience tools and resources to advance investigation of glycans and their roles in microbe-host interactions, immune-mediated diseases, and immune cell recognition and function. Future discoveries in these areas will increase fundamental scientific understanding and have the potential to improve diagnosis and treatment of infections and immune dysregulation.

scholarly journals Ail Binding to Fibronectin Facilitates Yersinia pestis Binding to Host Cells and Yop Delivery

2010 ◽  
Vol 78 (8) ◽  
pp. 3358-3368 ◽  
Author(s):  
Tiffany M. Tsang ◽  
Suleyman Felek ◽  
Eric S. Krukonis
Keyword(s):  
Escherichia Coli ◽  
Extracellular Matrix ◽  
Immune Responses ◽  
Yersinia Pestis ◽  
Matrix Protein ◽  
Host Cells ◽  
Extracellular Matrix Protein ◽  
Cell Binding ◽  
E Coli ◽  
Host Immune Responses

ABSTRACT Yersinia pestis, the causative agent of plague, evades host immune responses and rapidly causes disease. The Y. pestis adhesin Ail mediates host cell binding and is critical for Yop delivery. To identify the Ail receptor(s), Ail was purified following overexpression in Escherichia coli. Ail bound specifically to fibronectin, an extracellular matrix protein with the potential to act as a bridge between Ail and host cells. Ail expressed by E. coli also mediated binding to purified fibronectin, and Ail-mediated E. coli adhesion to host cells was dependent on fibronectin. Ail expressed by Y. pestis bound purified fibronectin, as did the Y. pestis adhesin plasminogen activator (Pla). However, a KIM5 Δail mutant had decreased binding to host cells, while a KIM5 Δpla mutant had no significant defect in adhesion. Furthermore, treatment with antifibronectin antibodies decreased Ail-mediated adhesion by KIM5 and the KIM5 Δpla mutant, indicating that the Ail-fibronectin interaction was important for cell binding. Finally, antifibronectin antibodies inhibited the KIM5-mediated cytotoxicity of host cells in an Ail-dependent fashion. These data indicate that Ail is a key adhesin that mediates binding to host cells through interaction with fibronectin on the surface of host cells, and this interaction is important for Yop delivery by Y. pestis.

scholarly journals Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyan clinical isolate defines a core parasite secretome

2017 ◽  
Vol 2 ◽  
pp. 50 ◽  
Author(s):  
Abdirahman Abdi ◽  
Lu Yu ◽  
David Goulding ◽  
Martin K. Rono ◽  
Philip Bejon ◽  
...  
Keyword(s):  
Clinical Isolate ◽  
Extracellular Vesicles ◽  
Genetic Material ◽  
Host Cells ◽  
Mass Spectrometry Data ◽  
Host Interactions ◽  
Effector Molecules ◽  
Host Immune Responses ◽  
Short Period

Background: Many pathogens secrete effector molecules to subvert host immune responses, to acquire nutrients, and/or to prepare host cells for invasion. One of the ways that effector molecules are secreted is through extracellular vesicles (EVs) such as exosomes. Recently, the malaria parasite P. falciparum has been shown to produce EVs that can mediate transfer of genetic material between parasites and induce sexual commitment. Characterizing the content of these vesicles may improve our understanding of P. falciparum pathogenesis and virulence. Methods: Previous studies of P. falciparum EVs have been limited to long-term adapted laboratory isolates. In this study, we isolated EVs from a Kenyan P. falciparum clinical isolate adapted to in vitro culture for a short period and characterized their protein content by mass spectrometry (data are available via ProteomeXchange, with identifier PXD006925). Results: We show that P. falciparum extracellular vesicles (PfEVs) are enriched in proteins found within the exomembrane compartments of infected erythrocytes such as Maurer’s clefts (MCs), as well as the secretory endomembrane compartments in the apical end of the merozoites, suggesting that these proteins play a role in parasite-host interactions. Comparison of this novel clinically relevant dataset with previously published datasets helps to define a core secretome present in Plasmodium EVs. Conclusions: P. falciparum extracellular vesicles contain virulence-associated parasite proteins. Therefore, analysis of PfEVs contents from a range of clinical isolates, and their functional validation may improve our understanding of the virulence mechanisms of the parasite, and potentially identify targets for interventions or diagnostics.

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