scholarly journals Determinants of Phagosomal pH During Host-Pathogen Interactions

2021 ◽  
Vol 8 ◽  
Author(s):  
Johannes Westman ◽  
Sergio Grinstein
Keyword(s):  
Host Cell ◽  
Microbial Growth ◽  
Intracellular Pathogens ◽  
Ion Permeation ◽  
Host Pathogen Interactions ◽  
Counter Ion ◽  
Regulatory Machinery ◽  
Different Types ◽  
Host Pathogen ◽  
Luminal Ph

The ability of phagosomes to halt microbial growth is intimately linked to their ability to acidify their luminal pH. Establishment and maintenance of an acidic lumen requires precise co-ordination of H+ pumping and counter-ion permeation to offset the countervailing H+ leakage. Despite the best efforts of professional phagocytes, however, a number of specialized pathogens survive and even replicate inside phagosomes. In such instances, pathogens target the pH-regulatory machinery of the host cell in an effort to survive inside or escape from phagosomes. This review aims to describe how phagosomal pH is regulated during phagocytosis, why it varies in different types of professional phagocytes and the strategies developed by prototypical intracellular pathogens to manipulate phagosomal pH to survive, replicate, and eventually escape from the phagocyte.

scholarly journals The Small GTPase Arf6: An Overview of Its Mechanisms of Action and of Its Role in Host–Pathogen Interactions and Innate Immunity

2019 ◽  
Vol 20 (9) ◽  
pp. 2209 ◽  
Author(s):  
Tim Van Acker ◽  
Jan Tavernier ◽  
Frank Peelman
Keyword(s):  
Innate Immunity ◽  
Phospholipase D ◽  
Actin Polymerization ◽  
Mechanisms Of Action ◽  
Vesicular Trafficking ◽  
Small Gtpase ◽  
Host Pathogen Interactions ◽  
Nadph Oxidases ◽  
Different Types ◽  
Host Pathogen

The small GTase Arf6 has several important functions in intracellular vesicular trafficking and regulates the recycling of different types of cargo internalized via clathrin-dependent or -independent endocytosis. It activates the lipid modifying enzymes PIP 5-kinase and phospholipase D, promotes actin polymerization, and affects several functionally distinct processes in the cell. Arf6 is used for the phagocytosis of pathogens and can be directly or indirectly targeted by various pathogens to block phagocytosis or induce the uptake of intracellular pathogens. Arf6 is also used in the signaling of Toll-like receptors and in the activation of NADPH oxidases. In this review, we first give an overview of the different roles and mechanisms of action of Arf6 and then focus on its role in innate immunity and host–pathogen interactions.

scholarly journals Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jonas Kjellin ◽  
Maria Pränting ◽  
Frauke Bach ◽  
Roshan Vaid ◽  
Bart Edelbroek ◽  
...  
Keyword(s):  
Dictyostelium Discoideum ◽  
High Throughput ◽  
Legionella Pneumophila ◽  
Transcriptional Response ◽  
Infection Model ◽  
Intracellular Pathogens ◽  
Host Pathogen Interactions ◽  
Human Macrophages ◽  
Wide Range ◽  
Host Pathogen

Abstract Background During infection by intracellular pathogens, a highly complex interplay occurs between the infected cell trying to degrade the invader and the pathogen which actively manipulates the host cell to enable survival and proliferation. Many intracellular pathogens pose important threats to human health and major efforts have been undertaken to better understand the host-pathogen interactions that eventually determine the outcome of the infection. Over the last decades, the unicellular eukaryote Dictyostelium discoideum has become an established infection model, serving as a surrogate macrophage that can be infected with a wide range of intracellular pathogens. In this study, we use high-throughput RNA-sequencing to analyze the transcriptional response of D. discoideum when infected with Mycobacterium marinum and Legionella pneumophila. The results were compared to available data from human macrophages. Results The majority of the transcriptional regulation triggered by the two pathogens was found to be unique for each bacterial challenge. Hallmark transcriptional signatures were identified for each infection, e.g. induction of endosomal sorting complexes required for transport (ESCRT) and autophagy genes in response to M. marinum and inhibition of genes associated with the translation machinery and energy metabolism in response to L. pneumophila. However, a common response to the pathogenic bacteria was also identified, which was not induced by non-pathogenic food bacteria. Finally, comparison with available data sets of regulation in human monocyte derived macrophages shows that the elicited response in D. discoideum is in many aspects similar to what has been observed in human immune cells in response to Mycobacterium tuberculosis and L. pneumophila. Conclusions Our study presents high-throughput characterization of D. discoideum transcriptional response to intracellular pathogens using RNA-seq. We demonstrate that the transcriptional response is in essence distinct to each pathogen and that in many cases, the corresponding regulation is recapitulated in human macrophages after infection by mycobacteria and L. pneumophila. This indicates that host-pathogen interactions are evolutionary conserved, derived from the early interactions between free-living phagocytic cells and bacteria. Taken together, our results strengthen the use of D. discoideum as a general infection model.

scholarly journals Silica-coated phosphorescent nanoprobes for selective cell targeting and dynamic bioimaging of pathogen–host cell interactions

2020 ◽  
Vol 56 (51) ◽  
pp. 6989-6992 ◽  
Author(s):  
Federico Iovino ◽  
Padryk Merkl ◽  
Anastasia Spyrogianni ◽  
Birgitta Henriques-Normark ◽  
Georgios A. Sotiriou
Keyword(s):  
Host Cell ◽  
Dynamic Imaging ◽  
Cell Interactions ◽  
Cell Targeting ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
Host Cell Interactions

Optically stable nanophosphors coated with a nanothin amorphous SiO2 layer allow for dynamic imaging of cell host–pathogen interactions. The SiO2 layer facilitates the functionalization of the nanoprobes with antibodies for selective cell targeting.

scholarly journals Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Laura A. L. Dillon ◽  
Rahul Suresh ◽  
Kwame Okrah ◽  
Hector Corrada Bravo ◽  
David M. Mosser ◽  
...  
Keyword(s):  
Host Cell ◽  
Leishmania Major ◽  
Transcriptional Profiling ◽  
Murine Macrophage ◽  
Host Pathogen Interactions ◽  
Host Pathogen

scholarly journals Metabolic labeling probes for interrogation of the host–pathogen interaction

2021 ◽  
Author(s):  
Bob J. Ignacio ◽  
Thomas Bakkum ◽  
Kimberly M. Bonger ◽  
Nathaniel I. Martin ◽  
Sander I. van Kasteren
Keyword(s):  
Intracellular Pathogens ◽  
Metabolic Labeling ◽  
Host Pathogen Interactions ◽  
Host Pathogen Interaction ◽  
New Methods ◽  
Host Pathogen

Metabolic labeling of intracellular pathogens can provide new methods of studying host pathogen interactions.

scholarly journals Lipids in host–pathogen interactions: Pathogens exploit the complexity of the host cell lipidome

2010 ◽  
Vol 49 (1) ◽  
pp. 1-26 ◽  
Author(s):  
Ynske P.M. van der Meer-Janssen ◽  
Josse van Galen ◽  
Joseph J. Batenburg ◽  
J. Bernd Helms
Keyword(s):  
Host Cell ◽  
Host Pathogen Interactions ◽  
Host Pathogen

scholarly journals Proteomic identification of Coxiella burnetii effector proteins targeted to the host cell mitochondria during infection

2020 ◽  
Author(s):  
Laura F. Fielden ◽  
Nichollas E. Scott ◽  
Catherine S. Palmer ◽  
Chen Ai Khoo ◽  
Hayley J Newton ◽  
...  
Keyword(s):  
Host Cell ◽  
Coxiella Burnetii ◽  
Q Fever ◽  
Bacterial Pathogens ◽  
Effector Proteins ◽  
Effector Protein ◽  
Subcellular Localisation ◽  
Host Pathogen Interactions ◽  
Affinity Enrichment ◽  
Host Pathogen

AbstractModulation of the host cell is integral to the survival and replication of microbial pathogens. Several intracellular bacterial pathogens deliver a cohort of bacterial proteins, termed ‘effector proteins’ into the host cell during infection by sophisticated protein translocation systems which manipulate cellular processes and functions. Despite the importance of these proteins during infection the functional contribution of individual effectors is poorly characterised, particularly in intracellular bacterial pathogens with large effector protein repertoires. Technical caveats have limited the capacity to study these proteins during a native infection, with many effector proteins having only been demonstrated to be translocated during over-expression of tagged versions. Here we present development of a novel strategy to examine effector proteins in the context of infection. We coupled a broad, unbiased proteomics-based screen with organelle purification to study the host-pathogen interactions occurring between the host cell mitochondrion and the Gram-negative, Q fever pathogen Coxiella burnetii. We identify 4 novel mitochondrially-targeted C. burnetii effector proteins, renamed Mitochondrial Coxiella effector protein (Mce) B to E. Examination of the subcellular localisation of ectopically expressed proteins in epithelial cells confirmed the mitochondrial localisation, demonstrating the robustness of our approach. Subsequent biochemical analysis and affinity enrichment proteomics of one of these effector proteins, MceC, revealed the protein is imported into mitochondria and can interact with components of the mitochondrial quality control machinery. Our study adapts high-sensitivity proteomics to the study of intracellular host-pathogen interactions occurring during infection, providing a robust strategy to examine the sub-cellular localisation of effector proteins during native infection. This approach could be applied to a range of pathogens and host cell compartments to provide a rich map of effector dynamics throughout infection.

scholarly journals The Ubiquitination System within Bacterial Host–Pathogen Interactions

2021 ◽  
Vol 9 (3) ◽  
pp. 638
Author(s):  
Vera Vozandychova ◽  
Pavla Stojkova ◽  
Kamil Hercik ◽  
Pavel Rehulka ◽  
Jiri Stulik
Keyword(s):  
Host Cell ◽  
Legionella Pneumophila ◽  
Pathogenic Bacteria ◽  
Vaccine Development ◽  
Shigella Flexneri ◽  
Effector Proteins ◽  
Deubiquitinating Enzymes ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
Ubiquitination System

Ubiquitination of proteins, like phosphorylation and acetylation, is an important regulatory aspect influencing numerous and various cell processes, such as immune response signaling and autophagy. The study of ubiquitination has become essential to learning about host–pathogen interactions, and a better understanding of the detailed mechanisms through which pathogens affect ubiquitination processes in host cell will contribute to vaccine development and effective treatment of diseases. Pathogenic bacteria (e.g., Salmonella enterica, Legionella pneumophila and Shigella flexneri) encode many effector proteins, such as deubiquitinating enzymes (DUBs), targeting the host ubiquitin machinery and thus disrupting pertinent ubiquitin-dependent anti-bacterial response. We focus here upon the host ubiquitination system as an integral unit, its interconnection with the regulation of inflammation and autophagy, and primarily while examining pathogens manipulating the host ubiquitination system. Many bacterial effector proteins have already been described as being translocated into the host cell, where they directly regulate host defense processes. Due to their importance in pathogenic bacteria progression within the host, they are regarded as virulence factors essential for bacterial evasion. However, in some cases (e.g., Francisella tularensis) the host ubiquitination system is influenced by bacterial infection, although the responsible bacterial effectors are still unknown.

scholarly journals Cellular metabolism in the defense against microbes

2021 ◽  
Vol 134 (5) ◽  
pp. jcs252023
Author(s):  
Lena Pernas
Keyword(s):  
Host Cell ◽  
Cell Metabolism ◽  
Critical Role ◽  
Cellular Metabolism ◽  
Human Metabolism ◽  
Host Pathogen Interactions ◽  
Nutrient Sources ◽  
Microbial Invasion ◽  
Host Pathogen ◽  
Host Metabolism

ABSTRACTThe study of metabolic changes associated with host–pathogen interactions have largely focused on the strategies that microbes use to subvert host metabolism to support their own proliferation. However, recent reports demonstrate that changes in host cell metabolism can also be detrimental to pathogens and restrict their growth. In this Review, I present a framework to consider how the host cell exploits the multifaceted roles of metabolites to defend against microbes. I also highlight how the rewiring of metabolic processes can strengthen cellular barriers to microbial invasion, regulate microbial virulence programs and factors, limit microbial access to nutrient sources and generate toxic environments for microbes. Collectively, the studies described here support a critical role for the rewiring of cellular metabolism in the defense against microbes. Further study of host–pathogen interactions from this framework has the potential to reveal novel aspects of host defense and metabolic control, and may inform how human metabolism impacts the progression of infectious disease.

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