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Microorganisms
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Interaction between Francisella Species and the Host Immune System
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Interaction between Francisella Species and the Host Immune System

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 26001

Special Issue Editors

Prof. Dr. Ales Macela

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Guest Editor
University of Defence, Brno, Czech Republic
Interests: immunology; innate immunity; infection biology; intracellular bacterial pathogens; Francisella tularensis; biological response modifiers
Dr. Klara Kubelkova

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Co-Guest Editor
University of Defence, Brno, Czech Republic
Interests: immunology; innate immunity; infection biology; intracellular bacterial pathogens; Francisella tularensis; biological response modifiers

Special Issue Information

Dear Colleagues,

More than a century of research on Francisella tularensis, the etiological agent of tularemia, has provided significant information on the bacterium itself and its relationship with its host. However, recently the genus Francisella contains at least ten species and the taxonomy of the whole genus is somewhat uncertain. Moreover, we still have substantial gaps in our understanding of the bacterium’s defense systems which enable its pathogenicity and virulence and of its complex interactions with the components of the host’s immune system. Recent advances in infection biology utilizing high-throughput technologies and sophisticated cell biology models and tools have brought new insights into the Francisella–host immune system relationship. Francisella species with their general and specific molecular and functional characteristics seems to be a promising model for host–pathogen interaction studies. 

The aim of this Special Issue is to provide new knowledge and enable a better understanding of the cellular and molecular events that lead 1) to Francisella sp. induced infection and 2) to the induction of protective immunity. Deciphering the extracellular and intracellular mutual interactions between Francisella and the host’s molecular and cellular entities leading to immune recognition, activation of innate immunity, induction of adaptive immune response, and elimination of bacteria from the cells and tissues is absolutely necessary for the construction of an effective vaccine, which is still lacking.

Prof. Dr. Ales Macela
Dr. Klara Kubelkova
Guest Editors

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Keywords

  • Francisella sp.
  • virulence factors
  • pathogen associated molecular patterns
  • innate immunity
  • adaptive immunity
  • cell subtypes
  • cell organelles
  • pattern recognition receptors
  • antibodies
  • cytokines
  • chemokines
  • signaling pathways

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Published Papers (5 papers)

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Research

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40 pages, 1727 KiB  
Article
Novel Transcriptional and Translational Biomarkers of Tularemia Vaccine Efficacy in a Mouse Inhalation Model: Proof of Concept
by Qing Yan Liu, Sonia Leclerc, Youlian Pan, Ziying Liu, Felicity Stark and Joseph Wayne Conlan
Microorganisms 2022, 10(1), 36; https://doi.org/10.3390/microorganisms10010036 - 26 Dec 2021
Cited by 1 | Viewed by 2654
Abstract
Francisella tularensis subspecies tularensis (Ftt) is extremely virulent for humans when inhaled as a small particle aerosol (<5 µm). Inhalation of ≥20 viable bacteria is sufficient to initiate infection with a mortality rate ≥30%. Consequently, in the past, Ftt became a primary [...] Read more.
Francisella tularensis subspecies tularensis (Ftt) is extremely virulent for humans when inhaled as a small particle aerosol (<5 µm). Inhalation of ≥20 viable bacteria is sufficient to initiate infection with a mortality rate ≥30%. Consequently, in the past, Ftt became a primary candidate for biological weapons development. To counter this threat, the USA developed a live vaccine strain (LVS), that showed efficacy in humans against inhalation of virulent Ftt. However, the breakthrough dose was fairly low, and protection waned with time. These weaknesses triggered extensive research for better vaccine candidates. Previously, we showed that deleting the clpB gene from virulent Ftt strain, SCHU S4, resulted in a mutant that was significantly less virulent than LVS for mice, yet better protected them from aerosol challenge with wild-type SCHU S4. To date, comprehensive searches for correlates of protection for SCHU S4 ΔclpB among molecules that are critical signatures of cell-mediated immunity, have yielded little reward. In this study we used transcriptomics analysis to expand the potential range of molecular correlates of protection induced by vaccination with SCHU S4 ΔclpB beyond the usual candidates. The results provide proof-of-concept that unusual host responses to vaccination can potentially serve as novel efficacy biomarkers for new tularemia vaccines. Full article
(This article belongs to the Special Issue Interaction between Francisella Species and the Host Immune System)
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Review

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13 pages, 314 KiB  
Review
Host Immunity and Francisella tularensis: A Review of Tularemia in Immunocompromised Patients
by Olivier Bahuaud, Cécile Le Brun and Adrien Lemaignen
Microorganisms 2021, 9(12), 2539; https://doi.org/10.3390/microorganisms9122539 - 8 Dec 2021
Cited by 9 | Viewed by 2796
Abstract
Tularemia, caused by the bacterium Francisella tularensis, is an infrequent zoonotic infection, well known in immunocompetent (but poorly described in immunocompromised) patients. Although there is no clear literature data about the specific characteristics of this disease in immunocompromised patients, clinical reports seem to [...] Read more.
Tularemia, caused by the bacterium Francisella tularensis, is an infrequent zoonotic infection, well known in immunocompetent (but poorly described in immunocompromised) patients. Although there is no clear literature data about the specific characteristics of this disease in immunocompromised patients, clinical reports seem to describe a different presentation of tularemia in these patients. Moreover, atypical clinical presentations added to the fastidiousness of pathogen identification seem to be responsible for a delayed diagnosis, leading to a” loss of chance” for immunocompromised patients. In this article, we first provide an overview of the host immune responses to Francisella infections and discuss how immunosuppressive therapies or diseases can lead to a higher susceptibility to tularemia. Then, we describe the particular clinical patterns of tularemia in immunocompromised patients from the literature. We also provide hints of an alternative diagnostic strategy regarding these patients. In conclusion, tularemia should be considered in immunocompromised patients presenting pulmonary symptoms or unexplained fever. Molecular techniques on pathological tissues might improve diagnosis with faster results. Full article
(This article belongs to the Special Issue Interaction between Francisella Species and the Host Immune System)
16 pages, 367 KiB  
Review
Francisella and Antibodies
by Klara Kubelkova and Ales Macela
Microorganisms 2021, 9(10), 2136; https://doi.org/10.3390/microorganisms9102136 - 12 Oct 2021
Cited by 4 | Viewed by 2040
Abstract
Immune responses to intracellular pathogens depend largely upon the activation of T helper type 1-dependent mechanisms. The contribution of B cells to establishing protective immunity has long been underestimated. Francisella tularensis, including a number of subspecies, provides a suitable model for the [...] Read more.
Immune responses to intracellular pathogens depend largely upon the activation of T helper type 1-dependent mechanisms. The contribution of B cells to establishing protective immunity has long been underestimated. Francisella tularensis, including a number of subspecies, provides a suitable model for the study of immune responses against intracellular bacterial pathogens. We previously demonstrated that Francisella infects B cells and activates B-cell subtypes to produce a number of cytokines and express the activation markers. Recently, we documented the early production of natural antibodies as a consequence of Francisella infection in mice. Here, we summarize current knowledge on the innate and acquired humoral immune responses initiated by Francisella infection and their relationships with the immune defense systems. Full article
(This article belongs to the Special Issue Interaction between Francisella Species and the Host Immune System)
22 pages, 1850 KiB  
Review
The Ubiquitination System within Bacterial Host–Pathogen Interactions
by Vera Vozandychova, Pavla Stojkova, Kamil Hercik, Pavel Rehulka and Jiri Stulik
Microorganisms 2021, 9(3), 638; https://doi.org/10.3390/microorganisms9030638 - 19 Mar 2021
Cited by 24 | Viewed by 5313
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Interaction between Francisella Species and the Host Immune System)
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Other

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4 pages, 457 KiB  
Case Report
Isolation of Francisella tularensis from Skin Ulcer after a Tick Bite, Austria, 2020
by Mateusz Markowicz, Anna-Margarita Schötta, Freya Penatzer, Christoph Matscheko, Gerold Stanek, Hannes Stockinger and Josef Riedler
Microorganisms 2021, 9(7), 1407; https://doi.org/10.3390/microorganisms9071407 - 29 Jun 2021
Cited by 5 | Viewed by 12344
Abstract
Ulceroglandular tularemia is caused by the transmission of Francisella tularensis by arthropods to a human host. We report a case of tick-borne tularemia in Austria which was followed by an abscess formation in a lymph node, making drainage necessary. F. tularensis subsp. holarctica [...] Read more.
Ulceroglandular tularemia is caused by the transmission of Francisella tularensis by arthropods to a human host. We report a case of tick-borne tularemia in Austria which was followed by an abscess formation in a lymph node, making drainage necessary. F. tularensis subsp. holarctica was identified by PCR and multilocus sequence typing. Full article
(This article belongs to the Special Issue Interaction between Francisella Species and the Host Immune System)
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