Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
6.0
Journals
Cells
Special Issues
Autophagy in Antimicrobial Immunity
share announcement

Autophagy in Antimicrobial Immunity

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Autophagy".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 28644

Special Issue Editor

Prof. Dr. Annemarie H. Meijer

E-Mail Website
Guest Editor
Gorlaeus Laboratory, Institute of Biology Leiden (IBL), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands
Interests: innate immunity; infectious disease; intracellular pathogens; autophagy; Lc3-associated phagocytosis; mycobacterium; salmonella; zebrafish

Special Issue Information

Dear Colleagues,

Paradigm-shifting discoveries in the last fifteen years have revealed that autophagy plays a major role in the immune system, in addition to its well-known function in cellular homeostasis. Connections between autophagy defects and major disease phenotypes have spurred interest in the autophagy machinery as a potential therapeutic target. In the area of infectious diseases, autophagy modulation is now being explored as a novel approach to treat antibiotic-resistant infections. Autophagy has multiple functions in host defense: it targets intracellular microbes towards lysosomal degradation, helps restrict microbes in subcellular compartments, facilitates antimicrobial peptide delivery to these compartments, controls inflammation, and processes peptides for antigen presentation. There is strong evidence for the host defense function of different autophagy-mediated processes, including xenophagy and LC3-associated phagocytosis but pathogens, in turn, have evolved virulence mechanisms to evade autophagy or even exploit autophagic compartments as a replication niche. This Special Issue of Cells aims to improve our understanding of the autophagic mechanisms that target different pathogens, including viruses, bacteria, fungi and protozoa, and provide new insights into the strategies that these pathogens use to subvert autophagy. Increasing the knowledge basis in this frontier research area is essential for opening up new avenues to develop autophagy-based therapeutic strategies for infectious disease treatment.

Prof. Annemarie H. Meijer
Guest Editor

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. Cells is an international peer-reviewed open access semimonthly 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

  • autophagy
  • xenophagy
  • LC3-associated phagocytosis
  • host defense
  • innate immunity
  • intracellular pathogens

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

21 pages, 6890 KiB  
Article
Aggregatibacter actinomycetemcomitans Induces Autophagy in Human Junctional Epithelium Keratinocytes
by Emiliano Vicencio, Esteban M. Cordero, Bastián I. Cortés, Sebastián Palominos, Pedro Parra, Tania Mella, Constanza Henrríquez, Nelda Salazar, Gustavo Monasterio, Emilio A. Cafferata, Paola Murgas, Rolando Vernal and Cristian Cortez
Cells 2020, 9(5), 1221; https://doi.org/10.3390/cells9051221 - 14 May 2020
Cited by 12 | Viewed by 3540
Abstract
The adverse environmental conditions found in the periodontium during periodontitis pathogenesis stimulate local autophagy responses, mainly due to a continuous inflammatory response against the dysbiotic subgingival microbiome. The junctional epithelium represents the main site of the initial interaction between the host and the [...] Read more.
The adverse environmental conditions found in the periodontium during periodontitis pathogenesis stimulate local autophagy responses, mainly due to a continuous inflammatory response against the dysbiotic subgingival microbiome. The junctional epithelium represents the main site of the initial interaction between the host and the dysbiotic biofilm. Here, we investigated the role of autophagy in junctional epithelium keratinocytes (JEKs) in response to Aggregatibacter actinomycetemcomitans or its purified lipopolysaccharides (LPS). Immunofluorescence confocal analysis revealed an extensive nuclear translocation of transcription factor EB (TFEB) and consequently, an increase in autophagy markers and LC3-turnover assessed by immunoblotting and qRT-PCR. Correspondingly, challenged JEKs showed a punctuate cytosolic profile of LC3 protein contrasting with the diffuse distribution observed in untreated controls. Three-dimensional reconstructions of confocal images displayed a close association between intracellular bacteria and LC3-positive vesicles. Similarly, a close association between autophagic vesicles and the protein p62 was observed in challenged JEKs, indicating that p62 is the main adapter protein recruited during A. actinomycetemcomitans infection. Finally, the pharmacological inhibition of autophagy significantly increased the number of bacteria-infected cells as well as their death, similar to treatment with LPS. Our results indicate that A. actinomycetemcomitans infection induces autophagy in JEKs, and this homeostatic process has a cytoprotective effect on the host cells during the early stages of infection. Full article
(This article belongs to the Special Issue Autophagy in Antimicrobial Immunity)
►▼ Show Figures

Figure 1

17 pages, 2309 KiB  
Article
The Lipid Virulence Factors of Mycobacterium tuberculosis Exert Multilayered Control over Autophagy-Related Pathways in Infected Human Macrophages
by Aïcha Bah, Merlin Sanicas, Jérôme Nigou, Christophe Guilhot, Catherine Astarie-Dequeker and Isabelle Vergne
Cells 2020, 9(3), 666; https://doi.org/10.3390/cells9030666 - 9 Mar 2020
Cited by 27 | Viewed by 5604
Abstract
Autophagy is an important innate immune defense mechanism that controls Mycobacterium tuberculosis (Mtb) growth inside macrophages. Autophagy machinery targets Mtb-containing phagosomes via xenophagy after damage to the phagosomal membrane due to the Type VII secretion system Esx-1 or via LC3-associated [...] Read more.
Autophagy is an important innate immune defense mechanism that controls Mycobacterium tuberculosis (Mtb) growth inside macrophages. Autophagy machinery targets Mtb-containing phagosomes via xenophagy after damage to the phagosomal membrane due to the Type VII secretion system Esx-1 or via LC3-associated phagocytosis without phagosomal damage. Conversely, Mtb restricts autophagy-related pathways via the production of various bacterial protein factors. Although bacterial lipids are known to play strategic functions in Mtb pathogenesis, their role in autophagy manipulation remains largely unexplored. Here, we report that the lipid virulence factors sulfoglycolipids (SLs) and phthiocerol dimycocerosates (DIMs) control autophagy-related pathways through distinct mechanisms in human macrophages. Using knock-out and knock-in mutants of Mtb and Mycobacterium bovis BCG (Bacille Calmette Guerin) and purified lipids, we found that (i) Mtb mutants with DIM and SL deficiencies promoted functional autophagy via an MyD88-dependent and phagosomal damage-independent pathway in human macrophages; (ii) SLs limited this pathway by acting as TLR2 antagonists; (iii) DIMs prevented phagosomal damage-independent autophagy while promoting Esx-1-dependent xenophagy; (iv) and DIMs, but not SLs, limited the acidification of LC3-positive Mtb compartments. In total, our study reveals an unexpected and intricate role for Mtb lipid virulence factors in controlling autophagy-related pathways in human macrophages, thus providing further insight into the autophagy manipulation tactics deployed by intracellular bacterial pathogens. Full article
(This article belongs to the Special Issue Autophagy in Antimicrobial Immunity)
►▼ Show Figures

Figure 1

Review

Jump to: Research

15 pages, 1787 KiB  
Review
Autophagy and Lc3-Associated Phagocytosis in Zebrafish Models of Bacterial Infections
by Salomé Muñoz-Sánchez, Michiel van der Vaart and Annemarie H. Meijer
Cells 2020, 9(11), 2372; https://doi.org/10.3390/cells9112372 - 29 Oct 2020
Cited by 22 | Viewed by 5077
Abstract
Modeling human infectious diseases using the early life stages of zebrafish provides unprecedented opportunities for visualizing and studying the interaction between pathogens and phagocytic cells of the innate immune system. Intracellular pathogens use phagocytes or other host cells, like gut epithelial cells, as [...] Read more.
Modeling human infectious diseases using the early life stages of zebrafish provides unprecedented opportunities for visualizing and studying the interaction between pathogens and phagocytic cells of the innate immune system. Intracellular pathogens use phagocytes or other host cells, like gut epithelial cells, as a replication niche. The intracellular growth of these pathogens can be counteracted by host defense mechanisms that rely on the autophagy machinery. In recent years, zebrafish embryo infection models have provided in vivo evidence for the significance of the autophagic defenses and these models are now being used to explore autophagy as a therapeutic target. In line with studies in mammalian models, research in zebrafish has shown that selective autophagy mediated by ubiquitin receptors, such as p62, is important for host resistance against several bacterial pathogens, including Shigella flexneri, Mycobacterium marinum, and Staphylococcus aureus. Furthermore, an autophagy related process, Lc3-associated phagocytosis (LAP), proved host beneficial in the case of Salmonella Typhimurium infection but host detrimental in the case of S. aureus infection, where LAP delivers the pathogen to a replication niche. These studies provide valuable information for developing novel therapeutic strategies aimed at directing the autophagy machinery towards bacterial degradation. Full article
(This article belongs to the Special Issue Autophagy in Antimicrobial Immunity)
►▼ Show Figures

Figure 1

10 pages, 694 KiB  
Review
Crosstalk Between Autophagy and Hypoxia-Inducible Factor-1α in Antifungal Immunity
by Tim Quäschling, Dirk Friedrich, George S. Deepe, Jr. and Jan Rupp
Cells 2020, 9(10), 2150; https://doi.org/10.3390/cells9102150 - 23 Sep 2020
Cited by 11 | Viewed by 3547
Abstract
Modern medicine is challenged by several potentially severe fungal pathogens such as Aspergillus fumigatus, Candida albicans, or Histoplasma capsulatum. Though not all fungal pathogens have evolved as primary pathogens, opportunistic pathogens can still cause fatal infections in immuno-compromised patients. After [...] Read more.
Modern medicine is challenged by several potentially severe fungal pathogens such as Aspergillus fumigatus, Candida albicans, or Histoplasma capsulatum. Though not all fungal pathogens have evolved as primary pathogens, opportunistic pathogens can still cause fatal infections in immuno-compromised patients. After infection with these fungi, the ingestion and clearance by innate immune cells is an important part of the host immune response. Innate immune cells utilize two different autophagic pathways, the canonical pathway and the non-canonical pathway, also called microtubule-associated protein 1A/1B-light chain 3 (LC3) -associated pathway (LAP), to clear fungal pathogens from the intracellular environment. The outcome of autophagy-related host immune responses depends on the pathogen and cell type. Therefore, the understanding of underlying molecular mechanisms of autophagy is crucial for the development and improvement of antifungal therapies. One of those molecular mechanisms is the interaction of the transcription-factor hypoxia-inducible factor 1α (HIF-1α) with the autophagic immune response. During this review, we will focus on a comprehensive overview of the role of autophagy and HIF-1α on the outcome of fungal infections. Full article
(This article belongs to the Special Issue Autophagy in Antimicrobial Immunity)
►▼ Show Figures

Figure 1

31 pages, 1653 KiB  
Review
Nuclear Receptors as Autophagy-Based Antimicrobial Therapeutics
by Prashanta Silwal, Seungwha Paik, Sang Min Jeon and Eun-Kyeong Jo
Cells 2020, 9(9), 1979; https://doi.org/10.3390/cells9091979 - 27 Aug 2020
Cited by 8 | Viewed by 4062
Abstract
Autophagy is an intracellular process that targets intracellular pathogens for lysosomal degradation. Autophagy is tightly controlled at transcriptional and post-translational levels. Nuclear receptors (NRs) are a family of transcriptional factors that regulate the expression of gene sets involved in, for example, metabolic and [...] Read more.
Autophagy is an intracellular process that targets intracellular pathogens for lysosomal degradation. Autophagy is tightly controlled at transcriptional and post-translational levels. Nuclear receptors (NRs) are a family of transcriptional factors that regulate the expression of gene sets involved in, for example, metabolic and immune homeostasis. Several NRs show promise as host-directed anti-infectives through the modulation of autophagy activities by their natural ligands or small molecules (agonists/antagonists). Here, we review the roles and mechanisms of NRs (vitamin D receptors, estrogen receptors, estrogen-related receptors, and peroxisome proliferator-activated receptors) in linking immunity and autophagy during infection. We also discuss the potential of emerging NRs (REV-ERBs, retinoic acid receptors, retinoic acid-related orphan receptors, liver X receptors, farnesoid X receptors, and thyroid hormone receptors) as candidate antimicrobials. The identification of novel roles and mechanisms for NRs will enable the development of autophagy-adjunctive therapeutics for emerging and re-emerging infectious diseases. Full article
(This article belongs to the Special Issue Autophagy in Antimicrobial Immunity)
►▼ Show Figures

Figure 1

30 pages, 1327 KiB  
Review
Autophagy Augmentation to Alleviate Immune Response Dysfunction, and Resolve Respiratory and COVID-19 Exacerbations
by Garrett Pehote and Neeraj Vij
Cells 2020, 9(9), 1952; https://doi.org/10.3390/cells9091952 - 24 Aug 2020
Cited by 28 | Viewed by 6323
Abstract
The preservation of cellular homeostasis requires the synthesis of new proteins (proteostasis) and organelles, and the effective removal of misfolded or impaired proteins and cellular debris. This cellular homeostasis involves two key proteostasis mechanisms, the ubiquitin proteasome system and the autophagy–lysosome pathway. These [...] Read more.
The preservation of cellular homeostasis requires the synthesis of new proteins (proteostasis) and organelles, and the effective removal of misfolded or impaired proteins and cellular debris. This cellular homeostasis involves two key proteostasis mechanisms, the ubiquitin proteasome system and the autophagy–lysosome pathway. These catabolic pathways have been known to be involved in respiratory exacerbations and the pathogenesis of various lung diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and coronavirus disease-2019 (COVID-19). Briefly, proteostasis and autophagy processes are known to decline over time with age, cigarette or biomass smoke exposure, and/or influenced by underlying genetic factors, resulting in the accumulation of misfolded proteins and cellular debris, elevating apoptosis and cellular senescence, and initiating the pathogenesis of acute or chronic lung disease. Moreover, autophagic dysfunction results in an impaired microbial clearance, post-bacterial and/or viral infection(s) which contribute to the initiation of acute and recurrent respiratory exacerbations as well as the progression of chronic obstructive and restrictive lung diseases. In addition, the autophagic dysfunction-mediated cystic fibrosis transmembrane conductance regulator (CFTR) immune response impairment further exacerbates the lung disease. Recent studies demonstrate the therapeutic potential of novel autophagy augmentation strategies, in alleviating the pathogenesis of chronic obstructive or restrictive lung diseases and exacerbations such as those commonly seen in COPD, CF, ALI/ARDS and COVID-19. Full article
(This article belongs to the Special Issue Autophagy in Antimicrobial Immunity)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop