scholarly journals Peptidylarginine Deiminase Inhibition Abolishes the Production of Large Extracellular Vesicles From Giardia intestinalis, Affecting Host-Pathogen Interactions by Hindering Adhesion to Host Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Bruno Gavinho ◽  
Bruna Sabatke ◽  
Veronica Feijoli ◽  
Izadora Volpato Rossi ◽  
Janaina Macedo da Silva ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Giardia Intestinalis ◽  
Host Cells ◽  
Peptidylarginine Deiminase ◽  
Host Pathogen Interactions ◽  
Host Pathogen

scholarly journals Peptidylarginine Deiminase inhibition abolishes the production of large extracellular vesicles fromGiardia intestinalis, affecting host-pathogen interactions by hindering adhesion to host cells

2019 ◽  
Author(s):  
Bruno Gavinho ◽  
Izadora Volpato Rossi ◽  
Ingrid Evans-Osses ◽  
Sigrun Lange ◽  
Marcel Ivan Ramirez
Keyword(s):  
Extracellular Vesicles ◽  
Mammalian Cells ◽  
Deep Understanding ◽  
Arginine Deiminase ◽  
Host Cells ◽  
Peptidylarginine Deiminase ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
Pad Inhibitor

AbstractGiardia intestinalisis an anaerobic protozoan that is an important etiologic agent of inflammation-driven diarrhea worldwide. Although self-limiting, a deep understanding of the factors involved in the pathogenicity that produces the disruption of the intestinal barrier remains unknown. There is evidence that under diverse conditions, the parasite is capable of shedding extracellular vesicles (EVs) which could modulate the physiopathology of giardiasis. Here we describe new insights ofG. intestinalisEV production, revealing its capacity to shed two different enriched EV populations (large and small extracellular vesicles) and identified a relevant adhesion function associated only with the larger population. Our work also aimed at assessing the influences of two recently identified inhibitors of EV release in mammalian cells, namely peptidylarginine deiminase (PAD) inhibitor and cannabidiol (CBD), on EV release fromGiardiaand their putative effects on host-pathogen interactions. PAD-inhibitor Cl-amidine and CBD were both able to effectively reduce EV shedding, the PAD-inhibitor specifically affecting the release of large extracellular vesicles and interfering within vitrohost-pathogen interactions. The strong efficacy of the PAD-inhibitor onGiardiaEV release indicates a phylogenetically conserved pathway of PAD-mediated EV release, most likely affecting theGiardiaarginine deiminase (GiADI) homolog of mammalian PADs. While there is still much to learn aboutG. intestinalisinteraction with its host, our results suggest that large and small EVs may be differently involved in protozoa communication, and that EV-inhibitor treatment may be a novel strategy for recurrent giardiasis treatment.

scholarly journals AFM-Based Correlative Microscopy Illuminates Human Pathogens

2021 ◽  
Vol 11 ◽  
Author(s):  
Supriya V. Bhat ◽  
Jared D. W. Price ◽  
Tanya E. S. Dahms
Keyword(s):  
Optical Microscopy ◽  
Disease Transmission ◽  
Fitness Landscape ◽  
Host Cells ◽  
Full Potential ◽  
Correlative Microscopy ◽  
Human Pathogens ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
The Many

Microbes have an arsenal of virulence factors that contribute to their pathogenicity. A number of challenges remain to fully understand disease transmission, fitness landscape, antimicrobial resistance and host heterogeneity. A variety of tools have been used to address diverse aspects of pathogenicity, from molecular host-pathogen interactions to the mechanisms of disease acquisition and transmission. Current gaps in our knowledge include a more direct understanding of host-pathogen interactions, including signaling at interfaces, and direct phenotypic confirmation of pathogenicity. Correlative microscopy has been gaining traction to address the many challenges currently faced in biomedicine, in particular the combination of optical and atomic force microscopy (AFM). AFM, generates high-resolution surface topographical images, and quantifies mechanical properties at the pN scale under physiologically relevant conditions. When combined with optical microscopy, AFM probes pathogen surfaces and their physical and molecular interaction with host cells, while the various modes of optical microscopy view internal cellular responses of the pathogen and host. Here we review the most recent advances in our understanding of pathogens, recent applications of AFM to the field, how correlative AFM-optical microspectroscopy and microscopy have been used to illuminate pathogenicity and how these methods can reach their full potential for studying host-pathogen interactions.

scholarly journals The complex, bidirectional role of extracellular vesicles in infection

2021 ◽  
Author(s):  
Joni Renee White ◽  
Priscila Dauros-Singorenko ◽  
Jiwon Hong ◽  
Frédérique Vanholsbeeck ◽  
Anthony Phillips ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Bacterial Pathogens ◽  
Host Cells ◽  
Signalling Molecules ◽  
Host Pathogen ◽  
Domains Of Life

Cells from all domains of life release extracellular vesicles (EVs), packages that carry a cargo of molecules that participate in communication, co-ordination of population behaviours, virulence and immune response mechanisms. Mammalian EVs play an increasingly recognised role to fight infection, yet may also be commandeered to disseminate pathogens and enhance infection. EVs released by bacterial pathogens may deliver toxins to host cells, signalling molecules and new DNA to other bacteria, and act as decoys, protecting infecting bacteria from immune killing. In this review, we explore the role of EVs in infection from the perspective of both the pathogen and host, and highlight their importance in the host/pathogen relationship. We highlight proposed strategies for EVs in therapeutics, and call attention to areas where existing knowledge and evidence is lacking.

scholarly journals Development of caecaloids to study host–pathogen interactions: new insights into immunoregulatory functions of Trichuris muris extracellular vesicles in the caecum

2020 ◽  
Vol 50 (9) ◽  
pp. 707-718 ◽  
Author(s):  
María A. Duque-Correa ◽  
Fernanda Schreiber ◽  
Faye H. Rodgers ◽  
David Goulding ◽  
Sally Forrest ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Host Pathogen Interactions ◽  
Trichuris Muris ◽  
Host Pathogen

The Use of High Pressure Freezing and Freeze Substitution to Study Host–Pathogen Interactions in Fungal Diseases of Plants

2003 ◽  
Vol 9 (6) ◽  
pp. 522-531 ◽  
Author(s):  
C.W. Mims ◽  
Gail J. Celio ◽  
Elizabeth A. Richardson
Keyword(s):  
High Pressure ◽  
Cell Walls ◽  
Freeze Substitution ◽  
Fungal Diseases ◽  
Host Cells ◽  
High Pressure Freezing ◽  
Plant Interactions ◽  
Host Pathogen Interactions ◽  
Thin Sections ◽  
Host Pathogen

This article reports on the use of high pressure freezing followed by freeze substitution (HPF/FS) to study ultrastructural details of host–pathogen interactions in fungal diseases of plants. The specific host–pathogen systems discussed here include a powdery mildew infection of poinsettia and rust infections of daylily and Indian strawberry. The three pathogens considered here all attack the leaves of their hosts and produce specialized hyphal branches known as haustoria that invade individual host cells without killing them. We found that HPF/FS provided excellent preservation of both haustoria and host cells for all three host–pathogen systems. Preservation of fungal and host cell membranes was particularly good and greatly facilitated the detailed study of host–pathogen interfaces. In some instances, HPF/FS provided information that was not available in samples prepared for study using conventional chemical fixation. On the other hand, we did encounter various problems associated with the use of HPF/FS. Examples included freeze damage of samples, inconsistency of fixation in different samples, separation of plant cell cytoplasm from cell walls, breakage of cell walls and membranes, and splitting of thin sections. However, we believe that the outstanding preservation of ultrastructural details afforded by HPF/FS significantly outweighs these problems and we highly recommend the use of this fixation protocol for future studies of fungal host-plant interactions.

scholarly journals What’s so special about Giardia ventral flagella? Interspecies cross-reacting monoclonal antibody against Pneumocystis jiroveci reacts with cilia and sparks questions on host-pathogen interactions

2020 ◽  
Author(s):  
Ewert Linder
Keyword(s):  
Monoclonal Antibody ◽  
Cultured Cells ◽  
Giardia Intestinalis ◽  
Immunofluorescent Staining ◽  
Ependymal Cells ◽  
Host Pathogen Interactions ◽  
Human Lung Tissue ◽  
Pneumocystis Jiroveci ◽  
Host Pathogen ◽  
Target Epitope

AbstractA mouse monoclonal antibody (Moab 4B8) cross-reacting with cilia/flagella was obtained by immunization with Pneumocystis-infected human lung tissue. A key observation was that Moab 4B8 reacted with the ventral flagella of Giardia intestinalis, but not with the three other flagellar pairs of this protozoan. To further identify the 4B8 target, its distribution was studied by immunofluorescence staining of cells and tissues of various origin.The target epitope recognized by Moab 4B8 was found to be associated with structures rich in microtubules; e.g. the mitotic spindle of cultured cells, ciliated airway epithelia, Sertoli cells of the testis and ependymal cells lining brain ventricles. The conserved nature of the 4B8 target was further shown by its presence in cilia of metazoan Schistosome larva and the green alga Chlamydomonas reinhardtii. Absence of the 4B8 target from Trypanosomes and Leishmania flagella suggested that it is involved in some function not primarily related to motility. Its presence in only the ventral flagella of Giardia therefore provides a unique opportunity to elucidate the relationship between ciliary structure and function in the same organism.The observed locations of the 4B8 target in tissues and cells of various origin, suggest a similarity to annexins - and specifically to α-19-giardin. This raises the possibility that it is involved in intra-flagellar transport and provides a basis for further studies aiming at its identification.Author SummaryPneumocystis is a ubiquitous fungal organism apparently colonizing the lung at an early age to cause pneumonia only in individuals with an impaired immune system. In the alveolar spaces of such individuals, extensive and frequently fatal proliferation of the pathogen occurs. Pneumocystis has no known reservoir in nature and apparently is transmitted directly from infected individuals via an airborne route. Adaptation of this Ascomycotic fungus to a parasitic lifestyle during its evolution apparently resulted in dependence upon host nutrients, but little is known about this presumed adaptation process. In this report, a previously unrecognized constituent of human Pneumocystis is detected using a monoclonal anti-Pneumocystis jiroveci antibody (Moab 4B8) which was obtained as a by-product in the search for reagents useful in diagnostics. The Moab 4B8 was shown to react with Pneumocystis but also with cytoskeletal microtubules, e.g. in ciliated epithelia, but not ubiquitously a constituent of the conserved cilia/flagella axonemal structure. A striking example of the discriminating capacity of antibody 4B8 was seen in immunofluorescent staining of the protozoan Giardia intestinalis, where only one out of four flagellar pairs expresses the target epitope. This observation of flagellar heterogenicity provoked the question raised in the title of this report. It also provides the basis for the discussion, which arrives at suggestive evidence for the involvement of the described evolutionarily conserved target in host-pathogen interactions related to membrane transport.

scholarly journals MARTX Toxin-Stimulated Interplay between Human Cells and Vibrio vulnificus

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Byoung Sik Kim ◽  
Jong-Hwan Kim ◽  
Sanghyeon Choi ◽  
Shinhye Park ◽  
Eun-Young Lee ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Vibrio Vulnificus ◽  
Expression Profiles ◽  
Host Cells ◽  
Iron Limitation ◽  
Host Pathogen Interactions ◽  
Content Type ◽  
Host Pathogen ◽  
Ht 29

ABSTRACT To understand toxin-stimulated host-pathogen interactions, we performed dual-transcriptome sequencing experiments using human epithelial (HT-29) and differentiated THP-1 (dTHP-1) immune cells infected with the sepsis-causing pathogen Vibrio vulnificus (either the wild-type [WT] pathogen or a multifunctional-autoprocessing repeats-in-toxin [MARTX] toxin-deficient strain). Gene set enrichment analyses revealed MARTX toxin-dependent responses, including negative regulation of extracellular related kinase 1 (ERK1) and ERK2 (ERK1/2) signaling and cell cycle regulation in HT-29 and dTHP-1 cells, respectively. Further analysis of the expression of immune-related genes suggested that the MARTX toxin dampens immune responses in gut epithelial cells but accelerates inflammation and nuclear factor κB (NF-κB) signaling in immune cells. With respect to the pathogen, siderophore biosynthesis genes were significantly more highly expressed in WT V. vulnificus than in the MARTX toxin-deficient mutant upon infection of dTHP-1 cells. Consistent with these results, iron homeostasis genes that limit iron levels for invading pathogens were overexpressed in WT V. vulnificus-infected dTHP-1 cells. Taken together, these results suggest that MARTX toxin regulates host inflammatory responses during V. vulnificus infection while also countering host defense mechanisms such as iron limitation. IMPORTANCE V. vulnificus is an opportunistic human pathogen that can cause life-threatening sepsis in immunocompromised patients via seafood poisoning or wound infection. Among the toxic substances produced by this pathogen, the MARTX toxin greatly contributes to disease progression by promoting the dysfunction and death of host cells, which allows the bacteria to disseminate and colonize the host. In response to this, host cells mount a counterattack against the invaders by upregulating various defense genes. In this study, the gene expression profiles of both host cells and V. vulnificus were analyzed by RNA sequencing to gain a comprehensive understanding of host-pathogen interactions. Our results suggest that V. vulnificus uses the MARTX toxin to subvert host cell immune responses as well as to oppose host counterattacks such as iron limitation.

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