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Pathogens
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New Tools in 3D Host-pathogen Interactions
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New Tools in 3D Host-pathogen Interactions

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 23616

Special Issue Editors

Dr. Pasquale Marrazzo

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Guest Editor
Department of Medical and Surgical Sciences, “Alma Mater Studiorum” Università di Bologna, Bologna, Italy
Interests: stem cells; histological modeling of human tissues; three-dimensional (3D) cultures; perinatal stem cells; spheroids; organoids; antimicrobial factors; natural compounds; regenerative medicine; biomaterials
Special Issues, Collections and Topics in MDPI journals
Dr. Monica Cricca

E-Mail Website
Guest Editor
Dept. of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
Interests: filamentous fungus; Exosomes; immunocompromised hosts; antifungal drugs; invasive infections
Dr. Natalie Fischer

E-Mail Website
Guest Editor
Sciensano, Brussels, Belgium
Interests: Infectious Disease, Host-Microbe Interaction, Human Microbiome, Global Health, Mucosal Immunology
Dr. Claudia Nastasi

E-Mail Website
Guest Editor
IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
Interests: Immunology, Host-Microbe interaction, Microbial metabolites, Innate Immunity, cancer, Immunometabolism
Dr. Daniela Fusco

E-Mail Website
Guest Editor
Dept. of Infectious Diseases Epidemiology, Bernhard Nocht Institute for Tropical Medicine (BNITM), Hamburg, Germany
Interests: Global Health, Diagnostic in low resources settings, Infectious diseases, Diseases of poverty, laboratory medicine, laboratory and health systems, Neglected Tropical Diseases

Special Issue Information

Dear colleagues,

The global burden of infectious disease still represents one of the major threats to human health. It gravely influences the social and economic wellbeing of individuals across the world. The landscape of infectious agents is continuously changing, following the genetic rearrangement and emergence of new microbial pathogens. The emergence of antimicrobial resistance calls for new tools for diagnosis and surveillance. The development of new vaccines and antimicrobials collides with the data inconsistency, which can be attributed in part to the constraints of preclinical models, which offer limited predictability for human outcomes and health. Thanks to improvement in the bioengineering field, eukaryotic 3D in vitro or ex vivo culture systems are being developed, which have been demonstrated to mimic the in vivo features essential for establishing in vitro infections. 3D cell culture models fill the gap between 2D cell cultures and animal models by more accurately providing the in vivo microenvironment, and thereby contribute to the understanding of the fundamental mechanisms of human pathogens. Thus, 3D models overcome experimental limitations and can advance preclinical and translational research in the field of drug development and host–pathogen interactions. This Special Issue will focus on both antimicrobial drugs and the exploitation of 3D models for the discovery of molecular infection markers. Such models should address all steps of infection, from the initiation of host–pathogen interaction, pathogenesis and disease progression, to immune response and resolution of disease, in order to provide an improved set of markers useful for drug developers and clinicians. We invite researchers to contribute by submitting both original research articles as well as reviews aiming to summarize the state-of-the-art of the proposed topics. The omics-based selection of pathogenesis biomarkers in 3D cell models is also encouraged. We hope to highlight innovative approaches and recent methodologies including 3D cell cultures, with a special interest in stem cells’ involvement in pathogenesis, the role of extracellular matrix in infections, and novel antigen targets. Potential topics include but are not limited to the following:
Diagnostic and predictive biomarkers in 3D models of bacterial, viral, and fungal infection; organotypic cultures and infection models by organ-on-a-chip technology; the development of organoids and spheroids for the characterization of infection markers; the identification of biomarkers for pathogenicity and virulence in cultured tissue slices and bioprinted tissues; the development of 3D models which include immune system cells; immune markers associated with 3D models of infection; as well as 3D in silico models, protein structures, and 3D genome in the context of infection.

Dr. Pasquale Marrazzo
Dr. Monica Cricca
Dr. Natalie Fischer
Dr. Claudia Nastasi
Dr. Daniela Fusco
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • 3D cell model
  • host–pathogen interactions
  • 3D culture
  • organoid
  • organ-on-a-chip
  • organotypic culture
  • immune response
  • biomarker
  • disease model
  • infection model
  • cellular microbiology
  • global health

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

4 pages, 198 KiB  
Editorial
Host–Pathogen Interactions: Organotypic Cultures to Unravel the Mysteries of the Primordial Hostility among Organisms
by Pasquale Marrazzo, Natalie Fischer, Claudia Nastasi, Monica Cricca and Daniela Fusco
Pathogens 2022, 11(3), 362; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11030362 - 16 Mar 2022
Cited by 1 | Viewed by 2045
Abstract
The interaction of humans with microorganisms represents a subtle balance between harm and good [...] Full article
(This article belongs to the Special Issue New Tools in 3D Host-pathogen Interactions)

Research

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18 pages, 10760 KiB  
Article
In Vitro 3D Staphylococcus aureus Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells
by Marloes I. Hofstee, Anja Heider, Sonja Häckel, Caroline Constant, Martijn Riool, R. Geoff Richards, T. Fintan Moriarty and Sebastian A. J. Zaat
Pathogens 2021, 10(11), 1446; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111446 - 06 Nov 2021
Cited by 7 | Viewed by 3080
Abstract
Staphylococcus aureus is the main causative pathogen of subcutaneous, bone, and implant-related infections, forming structures known as staphylococcal abscess communities (SACs) within tissues that also contain immunosuppressive myeloid-derived suppressor cells (MDSCs). Although both SACs and MDSCs are present in chronic S. aureus infections, [...] Read more.
Staphylococcus aureus is the main causative pathogen of subcutaneous, bone, and implant-related infections, forming structures known as staphylococcal abscess communities (SACs) within tissues that also contain immunosuppressive myeloid-derived suppressor cells (MDSCs). Although both SACs and MDSCs are present in chronic S. aureus infections, it remains unknown whether SACs directly trigger MDSC expansion. To investigate this, a previously developed 3D in vitro SAC model was co-cultured with murine and human bone marrow cells. Subsequently, it was shown that SAC-exposed human CD11blow/− myeloid cells or SAC-exposed murine CD11b+ Gr-1+ cells were immunosuppressive mainly by reducing absolute CD4+ and CD8α+ T cell numbers, as shown in T cell proliferation assays and with flow cytometry. Monocytic MDSCs from mice with an S. aureus bone infection also strongly reduced CD4+ and CD8α+ T cell numbers. Using protein biomarker analysis and an immunoassay, we detected in SAC–bone marrow co-cultures high levels of GM-CSF, IL-6, VEGF, IL-1β, TNFα, IL-10, and TGF-β. Furthermore, SAC-exposed neutrophils expressed Arg-1 and SAC-exposed monocytes expressed Arg-1 and iNOS, as shown via immunofluorescent stains. Overall, this study showed that SACs cause MDSC expansion from bone marrow cells and identified possible mediators to target as an additional strategy for treating chronic S. aureus infections. Full article
(This article belongs to the Special Issue New Tools in 3D Host-pathogen Interactions)
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17 pages, 11318 KiB  
Article
Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model
by Giulia Pilla, Tao Wu, Christen Grassel, Jonathan Moon, Jennifer Foulke-Abel, Christoph M. Tang and Eileen M. Barry
Pathogens 2021, 10(9), 1079; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091079 - 25 Aug 2021
Cited by 5 | Viewed by 2941
Abstract
Shigella is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low–middle income countries. Shigella sonnei prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as [...] Read more.
Shigella is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low–middle income countries. Shigella sonnei prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as a significant public health concern. One strategy to combat drug resistance in S. sonnei is the development of effective vaccines. There is no licensed vaccine against Shigella, and development has been hindered by the lack of an effective small-animal model. In this work, we used human enteroids, for the first time, as a model system to evaluate a plasmid-stabilized S. sonnei live attenuated vaccine strain, CVD 1233-SP, and a multivalent derivative, CVD 1233-SP::CS2-CS3, which expresses antigens from enterotoxigenic Escherichia coli. The strains were also tested for immunogenicity and protective capacity in the guinea pig model, demonstrating their ability to elicit serum and mucosal antibody responses as well as protection against challenge with wild-type S. sonnei. These promising results highlight the utility of enteroids as an innovative preclinical model to evaluate Shigella vaccine candidates, constituting a significant advance for the development of preventative strategies against this important human pathogen. Full article
(This article belongs to the Special Issue New Tools in 3D Host-pathogen Interactions)
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17 pages, 4447 KiB  
Article
3D Cocultures of Osteoblasts and Staphylococcus aureus on Biomimetic Bone Scaffolds as a Tool to Investigate the Host–Pathogen Interface in Osteomyelitis
by Raffaella Parente, Valentina Possetti, Maria Lucia Schiavone, Elisabetta Campodoni, Ciro Menale, Mattia Loppini, Andrea Doni, Barbara Bottazzi, Alberto Mantovani, Monica Sandri, Anna Tampieri, Cristina Sobacchi and Antonio Inforzato
Pathogens 2021, 10(7), 837; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10070837 - 03 Jul 2021
Cited by 5 | Viewed by 2776
Abstract
Osteomyelitis (OM) is an infectious disease of the bone primarily caused by the opportunistic pathogen Staphylococcus aureus (SA). This Gram-positive bacterium has evolved a number of strategies to evade the immune response and subvert bone homeostasis, yet the underlying mechanisms remain poorly understood. [...] Read more.
Osteomyelitis (OM) is an infectious disease of the bone primarily caused by the opportunistic pathogen Staphylococcus aureus (SA). This Gram-positive bacterium has evolved a number of strategies to evade the immune response and subvert bone homeostasis, yet the underlying mechanisms remain poorly understood. OM has been modeled in vitro to challenge pathogenetic hypotheses in controlled conditions, thus providing guidance and support to animal experimentation. In this regard, traditional 2D models of OM inherently lack the spatial complexity of bone architecture. Three-dimensional models of the disease overcome this limitation; however, they poorly reproduce composition and texture of the natural bone. Here, we developed a new 3D model of OM based on cocultures of SA and murine osteoblastic MC3T3-E1 cells on magnesium-doped hydroxyapatite/collagen I (MgHA/Col) scaffolds that closely recapitulate the bone extracellular matrix. In this model, matrix-dependent effects were observed in proliferation, gene transcription, protein expression, and cell–matrix interactions both of the osteoblastic cell line and of bacterium. Additionally, these had distinct metabolic and gene expression profiles, compared to conventional 2D settings, when grown on MgHA/Col scaffolds in separate monocultures. Our study points to MgHA/Col scaffolds as biocompatible and bioactive matrices and provides a novel and close-to-physiology tool to address the pathogenetic mechanisms of OM at the host–pathogen interface. Full article
(This article belongs to the Special Issue New Tools in 3D Host-pathogen Interactions)
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Review

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18 pages, 649 KiB  
Review
Methodologies for Generating Brain Organoids to Model Viral Pathogenesis in the CNS
by Hannah K. Hopkins, Elizabeth M. Traverse and Kelli L. Barr
Pathogens 2021, 10(11), 1510; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111510 - 19 Nov 2021
Cited by 5 | Viewed by 3539
Abstract
(1) Background: The human brain is of interest in viral research because it is often the target of viruses. Neurological infections can result in consequences in the CNS, which can result in death or lifelong sequelae. Organoids modeling the CNS are notable because [...] Read more.
(1) Background: The human brain is of interest in viral research because it is often the target of viruses. Neurological infections can result in consequences in the CNS, which can result in death or lifelong sequelae. Organoids modeling the CNS are notable because they are derived from stem cells that differentiate into specific brain cells such as neural progenitors, neurons, astrocytes, and glial cells. Numerous protocols have been developed for the generation of CNS organoids, and our goal was to describe the various CNS organoid models available for viral pathogenesis research to serve as a guide to determine which protocol might be appropriate based on research goal, timeframe, and budget. (2) Methods: Articles for this review were found in Pubmed, Scopus and EMBASE. The search terms used were “brain + organoid” and “CNS + organoid” (3) Results: There are two main methods for organoid generation, and the length of time for organoid generation varied from 28 days to over 2 months. The costs for generating a population of organoids ranged from USD 1000 to 5000. (4) Conclusions: There are numerous methods for generating organoids representing multiple regions of the brain, with several types of modifications for fine-tuning the model to a researcher’s specifications. Organoid models of the CNS can serve as a platform for characterization and mechanistic studies that can reduce or eliminate the use of animals, especially for viruses that only cause disease in the human CNS. Full article
(This article belongs to the Special Issue New Tools in 3D Host-pathogen Interactions)
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21 pages, 389 KiB  
Review
Are the Organoid Models an Invaluable Contribution to ZIKA Virus Research?
by Pasquale Marrazzo, Monica Cricca and Claudia Nastasi
Pathogens 2021, 10(10), 1233; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10101233 - 24 Sep 2021
Cited by 6 | Viewed by 2888
Abstract
In order to prevent new pathogen outbreaks and avoid possible new global health threats, it is important to study the mechanisms of microbial pathogenesis, screen new antiviral agents and test new vaccines using the best methods. In the last decade, organoids have provided [...] Read more.
In order to prevent new pathogen outbreaks and avoid possible new global health threats, it is important to study the mechanisms of microbial pathogenesis, screen new antiviral agents and test new vaccines using the best methods. In the last decade, organoids have provided a groundbreaking opportunity for modeling pathogen infections in human brains, including Zika virus (ZIKV) infection. ZIKV is a member of the Flavivirus genus, and it is recognized as an emerging infectious agent and a serious threat to global health. Organoids are 3D complex cellular models that offer an in-scale organ that is physiologically alike to the original one, useful for exploring the mechanisms behind pathogens infection; additionally, organoids integrate data generated in vitro with traditional tools and often support those obtained in vivo with animal model. In this mini-review the value of organoids for ZIKV research is examined and sustained by the most recent literature. Within a 3D viewpoint, tissue engineered models are proposed as future biological systems to help in deciphering pathogenic processes and evaluate preventive and therapeutic strategies against ZIKV. The next steps in this field constitute a challenge that may protect people and future generations from severe brain defects. Full article
(This article belongs to the Special Issue New Tools in 3D Host-pathogen Interactions)
13 pages, 1175 KiB  
Review
Refining Host-Pathogen Interactions: Organ-on-Chip Side of the Coin
by Buket Baddal and Pasquale Marrazzo
Pathogens 2021, 10(2), 203; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10020203 - 13 Feb 2021
Cited by 22 | Viewed by 4269
Abstract
Bioinspired organ-level in vitro platforms that recapitulate human organ physiology and organ-specific responses have emerged as effective technologies for infectious disease research, drug discovery, and personalized medicine. A major challenge in tissue engineering for infectious diseases has been the reconstruction of the dynamic [...] Read more.
Bioinspired organ-level in vitro platforms that recapitulate human organ physiology and organ-specific responses have emerged as effective technologies for infectious disease research, drug discovery, and personalized medicine. A major challenge in tissue engineering for infectious diseases has been the reconstruction of the dynamic 3D microenvironment reflecting the architectural and functional complexity of the human body in order to more accurately model the initiation and progression of host–microbe interactions. By bridging the gap between in vitro experimental models and human pathophysiology and providing alternatives for animal models, organ-on-chip microfluidic devices have so far been implemented in multiple research areas, contributing to major advances in the field. Given the emergence of the recent pandemic, plug-and-play organ chips may hold the key for tackling an unmet clinical need in the development of effective therapeutic strategies. In this review, latest studies harnessing organ-on-chip platforms to unravel host–pathogen interactions are presented to highlight the prospects for the microfluidic technology in infectious diseases research. Full article
(This article belongs to the Special Issue New Tools in 3D Host-pathogen Interactions)
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