Virulence factors in brucellosis: implications for aetiopathogenesis and treatment

2007 ◽  
Vol 9 (35) ◽  
pp. 1-10 ◽  
Author(s):  
Emilie Fugier ◽  
Georgios Pappas ◽  
Jean-Pierre Gorvel
Keyword(s):  
Immune System ◽  
Animal Models ◽  
Host Cell ◽  
Virulence Factors ◽  
Zoonotic Disease ◽  
Host Immune System ◽  
Intracellular Pathogens ◽  
Virulence Regulator

Brucellaspecies are responsible for the global zoonotic disease brucellosis. These intracellular pathogens express a set of factors – including lipopolysaccharides, virulence regulator proteins and phosphatidylcholine – to ensure their full virulence. Some virulence factors are essential for invasion of the host cell, whereas others are crucial to avoid elimination by the host. They allowBrucellaspp. to survive and proliferate within its replicative vacuole and enable the bacteria to escape detection by the host immune system. Several strategies have been used to develop animal vaccines against brucellosis, but no adequate vaccine yet exists to cure the disease in humans. This is probably due to the complicated pathophysiology of humanBrucellaspp. infection, which is different than in animal models. Here we reviewBrucellaspp. virulence factors and how they control bacterial trafficking within the host cell.

scholarly journals Potential Roles of Fungal Extracellular Vesicles during Infection

mSphere ◽  
2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Luna S. Joffe ◽  
Leonardo Nimrichter ◽  
Marcio L. Rodrigues ◽  
Maurizio Del Poeta
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Cell Types ◽  
Fungal Diseases ◽  
Host Immune System ◽  
The Past ◽  
Invasive Fungal Diseases

ABSTRACT Extracellular vesicles (EVs) are produced by virtually all cell types. Within the past few years, work in this field has revealed more information about fungal EVs. Fungal EVs have been shown to carry proteins, lipids, pigments, polysaccharides, and RNA; these components are known virulence factors, a fact which supports the hypothesis that fungal EVs concentrate pathogenic determinants. Extracellular vesicles (EVs) are produced by virtually all cell types. Within the past few years, work in this field has revealed more information about fungal EVs. Fungal EVs have been shown to carry proteins, lipids, pigments, polysaccharides, and RNA; these components are known virulence factors, a fact which supports the hypothesis that fungal EVs concentrate pathogenic determinants. Additionally, recent studies have demonstrated that fungal EVs stimulate the host immune system. In this review, putative roles of fungal EVs are discussed, including their potential as vaccination tools and their possible contribution to pathogenesis in invasive fungal diseases.

scholarly journals Understanding GroEL and DnaK Stress Response Proteins as Antigens for Bacterial Diseases

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 773
Author(s):  
Kezia R. Fourie ◽  
Heather L. Wilson
Keyword(s):  
Immune System ◽  
Stress Response ◽  
Cell Surface ◽  
Virulence Factors ◽  
Cellular Localization ◽  
Vaccine Development ◽  
Host Immune System ◽  
A Cell ◽  
Stress Response Proteins ◽  
Shock Proteins

Bacteria do not simply express a constitutive panel of proteins but they instead undergo dynamic changes in their protein repertoire in response to changes in nutritional status and when exposed to different environments. These differentially expressed proteins may be suitable to use for vaccine antigens if they are virulence factors. Immediately upon entry into the host organism, bacteria are exposed to a different environment, which includes changes in temperature, osmotic pressure, pH, etc. Even when an organism has already penetrated the blood or lymphatics and it then enters another organ or a cell, it can respond to these new conditions by increasing the expression of virulence factors to aid in bacterial adherence, invasion, or immune evasion. Stress response proteins such as heat shock proteins and chaperones are some of the proteins that undergo changes in levels of expression and/or changes in cellular localization from the cytosol to the cell surface or the secretome, making them potential immunogens for vaccine development. Herein we highlight literature showing that intracellular chaperone proteins GroEL and DnaK, which were originally identified as playing a role in protein folding, are relocated to the cell surface or are secreted during invasion and therefore may be recognized by the host immune system as antigens. In addition, we highlight literature showcasing the immunomodulation effects these proteins can have on the immune system, also making them potential adjuvants or immunotherapeutics.

scholarly journals Prison Break: Pathogens' Strategies To Egress from Host Cells

2012 ◽  
Vol 76 (4) ◽  
pp. 707-720 ◽  
Author(s):  
Nikolas Friedrich ◽  
Monica Hagedorn ◽  
Dominique Soldati-Favre ◽  
Thierry Soldati
Keyword(s):  
Host Cell ◽  
Pathogenic Bacteria ◽  
Wide Spectrum ◽  
Host Cells ◽  
Host Immune System ◽  
Intracellular Pathogens ◽  
Pathogenic Yeast ◽  
Apicomplexan Parasites ◽  
Strategic Process ◽  
Intimate Association

SUMMARYA wide spectrum of pathogenic bacteria and protozoa has adapted to an intracellular life-style, which presents several advantages, including accessibility to host cell metabolites and protection from the host immune system. Intracellular pathogens have developed strategies to enter and exit their host cells while optimizing survival and replication, progression through the life cycle, and transmission. Over the last decades, research has focused primarily on entry, while the exit process has suffered from neglect. However, pathogen exit is of fundamental importance because of its intimate association with dissemination, transmission, and inflammation. Hence, to fully understand virulence mechanisms of intracellular pathogens at cellular and systemic levels, it is essential to consider exit mechanisms to be a key step in infection. Exit from the host cell was initially viewed as a passive process, driven mainly by physical stress as a consequence of the explosive replication of the pathogen. It is now recognized as a complex, strategic process termed “egress,” which is just as well orchestrated and temporally defined as entry into the host and relies on a dynamic interplay between host and pathogen factors. This review compares egress strategies of bacteria, pathogenic yeast, and kinetoplastid and apicomplexan parasites. Emphasis is given to recent advances in the biology of egress in mycobacteria and apicomplexans.

scholarly journals The InhA Metalloproteases of Bacillus cereus Contribute Concomitantly to Virulence

2009 ◽  
Vol 192 (1) ◽  
pp. 286-294 ◽  
Author(s):  
Elisabeth Guillemet ◽  
Céline Cadot ◽  
Seav-Ly Tran ◽  
Marie-Hélène Guinebretière ◽  
Didier Lereclus ◽  
...  
Keyword(s):  
Immune System ◽  
Stationary Phase ◽  
Bacillus Cereus ◽  
Virulence Factors ◽  
Time Course ◽  
Expression Profiles ◽  
Host Immune System ◽  
Strong Decrease ◽  
Peptide Cleavage ◽  
Transcriptional Fusions

ABSTRACT The virulence of Bacillus cereus requires that bacteria have the capacity to colonize their host, degrade specific tissues, and circumvent the host immune system. To study this aspect of pathogenesis, we focused on three metalloproteases, InhA1, InhA2, and InhA3, which share more than 66% identity. The expression of these metalloprotease genes was assessed by transcriptional fusions with a lacZ reporter gene. The expression profiles suggest a complementary time course of InhA production. Indeed, the genes are simultaneously expressed but are oppositely controlled during stationary phase. We constructed single and multiple inhA mutants and assessed the bacterial locations of the proteins as well as their individual or additive roles in macrophage escape and toxicity, antibacterial-peptide cleavage, and virulence. InhA1, a major component of the spore exosporium, is the only InhA metalloprotease involved in bacterial escape from macrophages. A mutant lacking inhA1, inhA2, and inhA3 shows a strong decrease in the level of virulence for insects. Taken together, these results show that the InhA metalloproteases of B. cereus are important virulence factors that may allow the bacteria to counteract the host immune system.

scholarly journals Investigation of Bartonella quintana Host Immune Evasion

2021 ◽  
Author(s):  
◽  
Callum Lambert
Keyword(s):  
Immune System ◽  
Actin Cytoskeleton ◽  
Host Cell ◽  
Immune Evasion ◽  
Mammalian Species ◽  
Effector Proteins ◽  
Host Cells ◽  
Sand Fly ◽  
Host Immune System ◽  
Bartonella Quintana

<p>Bartonella is a genus of gram-negative alphaproteobacteria that infect mammals, causing both acute and chronic disease. Bartonella are re-emerging infectious pathogens that cause a variety of clinical syndromes in humans worldwide, including cat scratch disease, trench fever, bacillary angiomatosis, and endocarditis. Bartonella spp. are spread by biting arthropods such as the sand fly, cat flea, and body louse, and have been isolated from almost all mammalian species tested. Bartonella are a re-emerging concern as the number of confirmed Bartonella diagnoses are increasing, primarily in immunocompromised groups, homeless populations, refugee camps, and in veterinary workers. The three primary human disease-causing Bartonella spp. are B. henselae, B. quintana, and B. bacilliformis. Bartonella are known to subvert the host immune system and persist within the host, often causing bacteraemia which is difficult to effectively diagnose and treat. B. quintana infects humans; after introduction to the skin the bacteria implement numerous immune evasion mechanisms to enter the bloodstream and invade erythrocytes. The mechanisms by which B. quintana modulates and evades the immune system during early infection are almost entirely unknown. Following exposure to B. quintana, the bacteria encounter host immune cells but survive, evading these cells and disseminating into the lymphatic system and eventually bloodstream. This thesis project aimed to dissect the interactions between B. quintana and the human innate immune system to better understand the early stages of infection. A gentamicin protection assay was developed to investigate the ability of THP-1 macrophages, representing human macrophages present in the skin, to internalise B. quintana. These data revealed THP-1 cells were unable to effectively internalise B. quintana, although the mechanism responsible was not determined. Subsequent experiments investigated the role of the B. quintana Type IV secreted effector protein BepA1 in the inhibition of internalisation. Bacterial effector proteins often pathogenically modulate host cell signalling to benefit the bacteria, i.e., altering the actin cytoskeleton to inhibit phagocytosis or supressing immune responses. It was hypothesised BepA1 could play a role in inhibiting phagocytosis; therefore, the host cell target of BepA1 was investigated with a yeast two-hybrid system assay. The human protein Myozap was uncovered as a potential protein that interacts with BepA1. Myozap is expressed in cardiac and lung tissue as well as epithelial and endothelial cells, where it modulates Rho-dependent actin signalling, potentially affecting the actin cytoskeleton and the transcription factor MRTF-A, which influences immune reaction through modulation of NF-κB. To investigate the functional effects of BepA1 activity in host cells, HeLa cells were transfected with BepA1; cell migration and cytokine secretion were assessed, revealing a decrease in pro-inflammatory cytokines in BepA1-transfected cells in response to TNF-a stimulation. These data suggest BepA1 may be deployed by B. quintana during infection to suppress the host immune response and avoid clearance from the site of infection. This research addressed a major gap in our understanding of B. quintana infections. Improving our understanding of the interactions between Bartonella and the host immune system is an essential first step in the development of improved diagnostic techniques and treatments.   </p>

scholarly journals Investigation of Bartonella quintana Host Immune Evasion

2021 ◽  
Author(s):  
◽  
Callum Lambert
Keyword(s):  
Immune System ◽  
Actin Cytoskeleton ◽  
Host Cell ◽  
Immune Evasion ◽  
Mammalian Species ◽  
Effector Proteins ◽  
Host Cells ◽  
Sand Fly ◽  
Host Immune System ◽  
Bartonella Quintana

<p>Bartonella is a genus of gram-negative alphaproteobacteria that infect mammals, causing both acute and chronic disease. Bartonella are re-emerging infectious pathogens that cause a variety of clinical syndromes in humans worldwide, including cat scratch disease, trench fever, bacillary angiomatosis, and endocarditis. Bartonella spp. are spread by biting arthropods such as the sand fly, cat flea, and body louse, and have been isolated from almost all mammalian species tested. Bartonella are a re-emerging concern as the number of confirmed Bartonella diagnoses are increasing, primarily in immunocompromised groups, homeless populations, refugee camps, and in veterinary workers. The three primary human disease-causing Bartonella spp. are B. henselae, B. quintana, and B. bacilliformis. Bartonella are known to subvert the host immune system and persist within the host, often causing bacteraemia which is difficult to effectively diagnose and treat. B. quintana infects humans; after introduction to the skin the bacteria implement numerous immune evasion mechanisms to enter the bloodstream and invade erythrocytes. The mechanisms by which B. quintana modulates and evades the immune system during early infection are almost entirely unknown. Following exposure to B. quintana, the bacteria encounter host immune cells but survive, evading these cells and disseminating into the lymphatic system and eventually bloodstream. This thesis project aimed to dissect the interactions between B. quintana and the human innate immune system to better understand the early stages of infection. A gentamicin protection assay was developed to investigate the ability of THP-1 macrophages, representing human macrophages present in the skin, to internalise B. quintana. These data revealed THP-1 cells were unable to effectively internalise B. quintana, although the mechanism responsible was not determined. Subsequent experiments investigated the role of the B. quintana Type IV secreted effector protein BepA1 in the inhibition of internalisation. Bacterial effector proteins often pathogenically modulate host cell signalling to benefit the bacteria, i.e., altering the actin cytoskeleton to inhibit phagocytosis or supressing immune responses. It was hypothesised BepA1 could play a role in inhibiting phagocytosis; therefore, the host cell target of BepA1 was investigated with a yeast two-hybrid system assay. The human protein Myozap was uncovered as a potential protein that interacts with BepA1. Myozap is expressed in cardiac and lung tissue as well as epithelial and endothelial cells, where it modulates Rho-dependent actin signalling, potentially affecting the actin cytoskeleton and the transcription factor MRTF-A, which influences immune reaction through modulation of NF-κB. To investigate the functional effects of BepA1 activity in host cells, HeLa cells were transfected with BepA1; cell migration and cytokine secretion were assessed, revealing a decrease in pro-inflammatory cytokines in BepA1-transfected cells in response to TNF-a stimulation. These data suggest BepA1 may be deployed by B. quintana during infection to suppress the host immune response and avoid clearance from the site of infection. This research addressed a major gap in our understanding of B. quintana infections. Improving our understanding of the interactions between Bartonella and the host immune system is an essential first step in the development of improved diagnostic techniques and treatments.   </p>

scholarly journals Cancer-Immunity Cycle and Therapeutic Interventions- Opportunities for Including Pet Dogs With Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Samantha K. Von Rueden ◽  
Timothy M. Fan
Keyword(s):  
Immune System ◽  
Animal Models ◽  
Tumor Formation ◽  
Therapeutic Interventions ◽  
Large Animal ◽  
Host Immune System ◽  
Host Immune Responses ◽  
Large Animal Models ◽  
Cancer Immunity ◽  
Dynamic Series

The tumor-immune interplay represents a dynamic series of events executed by cellular and soluble participants that either promote or inhibit successful tumor formation and growth. Throughout a tumor’s development and progression, the host organism’s immune system reacts by generating anti-cancer defenses through various incremental and combinatorial mechanisms, and this reactive orchestration is termed the cancer-immunity cycle. Success or failure of the cancer-immunity cycle dictates the fate of both host and tumor as winner or loser. Insights into how the tumor and host immune system continuously adapt to each other throughout the lifecycle of the tumor is necessary to rationally develop new effective immunotherapies. Additionally, the evolving nature of the cancer-immunity cycle necessitates therapeutic agility, requiring real-time serial assessment of immunobiologic markers that permits tailoring of therapies to the everchanging tumor immune microenvironment. In order to accelerate advances in the field of immuno-oncology, this review summarizes the steps comprising the cancer-immunity cycle, and underscores key breakpoints in the cycle that either favor cancer regression or progression, as well as shaping of the tumor microenvironment and associated immune phenotypes. Furthermore, specific large animal models of spontaneous cancers that are deemed immunogenic will be reviewed and proposed as unique resources for validating investigational immunotherapeutic protocols that are informed by the cancer-immunity cycle. Collectively, this review will provide a progressive look into the dynamic interplay between tumor and host immune responses and raise awareness for how large animal models can be included for developing combinatorial and sequenced immunotherapies to maximizing favorable treatment outcomes.

scholarly journals Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens

2007 ◽  
Vol 71 (4) ◽  
pp. 636-652 ◽  
Author(s):  
John H. Brumell ◽  
Marci A. Scidmore
Keyword(s):  
Host Cell ◽  
Bacterial Pathogens ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Rab Gtpase ◽  
Host Immune System ◽  
Intracellular Pathogens ◽  
Cell Trafficking ◽  
Rab Gtpases

SUMMARY Intracellular bacterial pathogens have evolved highly specialized mechanisms to enter and survive within their eukaryotic hosts. In order to do this, bacterial pathogens need to avoid host cell degradation and obtain nutrients and biosynthetic precursors, as well as evade detection by the host immune system. To create an intracellular niche that is favorable for replication, some intracellular pathogens inhibit the maturation of the phagosome or exit the endocytic pathway by modifying the identity of their phagosome through the exploitation of host cell trafficking pathways. In eukaryotic cells, organelle identity is determined, in part, by the composition of active Rab GTPases on the membranes of each organelle. This review describes our current understanding of how selected bacterial pathogens regulate host trafficking pathways by the selective inclusion or retention of Rab GTPases on membranes of the vacuoles that they occupy in host cells during infection.

scholarly journals Exploring the Modulation of Immune Response and Oxidative Stress of Intracellular Pathogens Using Nanoparticles Encapsulating Drugs

2020 ◽  
Author(s):  
Ramendra Pati Pandey ◽  
Anjali Priyadarshini ◽  
Archana Gupta ◽  
Arpana Vibhuti ◽  
Elcio Leal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Delivery ◽  
Immune Response ◽  
Immune System ◽  
Bacterial Infections ◽  
Reactive Nitrogen ◽  
Host Immune System ◽  
Intracellular Pathogens ◽  
Antioxidant Defences ◽  
And Oxidative Stress

The immune system is a dynamic network of cells and cytokines are the major mediators of immune responses which combat pathogens. Based on the cytokine production, effector T cells differentiate into subsets known as Th1, Th2, Th17 or Treg (T regulatory). This system serves as a barrier to intracellular pathogens, bacterial infections and stimulates the production of reactive oxygen species (ROS), reactive nitrogen intermediates (RNI) and nitric oxide (NO), which diffuses across membranes and engulfs intracellular pathogens. Oxidative stress occurs when ROS, reactive nitrogen species (RNS) production and antioxidant defences become imbalanced. Oxidative stress generated by infected cells produces a substantial amount of free radicals which enables killing of intracellular pathogens. Intracellular pathogens are exposed to endogenous ROS as part of normal aerobic respiration, also aexogenous ROS and RNS are generated by the host immune system in response to infection. Nanoparticles which are designed for drug delivery are capable of trapping the desired drug in the particles which protects the drug from enzymatic degradation in a biological system. The small (subcellular) size of nanoparticles enables higher intracellular uptake of the drug which results in the reduction of the concentration of free drugs reducing their toxic effect. Research on the modulation of immune response and oxidative stress using nanoparticles used to encapsulate drugs has yet to be explored fully. In this review we illustrate the immune activation and generation of oxidative stress properties which are mediated by nanoparticle encapsulated drug delivery systems which can make the therapy more effective in case of diseases caused by intracellular pathogens.

scholarly journals VARIABILITY OF NEUTROPHIL-ACTIVATING PROTEIN AMONG HELICOBACTER PYLORI STRAINS

2021 ◽  
Vol 80 (1) ◽  
pp. 43-50
Author(s):  
Cecília R.C. Calado
Keyword(s):  
Genetic Diversity ◽  
Helicobacter Pylori ◽  
Immune System ◽  
Virulence Factors ◽  
Immunomodulatory Activity ◽  
Host Immune System ◽  
High Genetic Diversity ◽  
Vacuolating Cytotoxin ◽  
Synonymous Substitutions ◽  
H Pylori

The Helicobacter pylori neutrophil activating protein (NAP) presents relevant inflammatory and immunomodulatory activity and has consequently been explored as a diagnosis and therapeutic target. In the present work, nap gene sequences, retrieved from H. pylori isolated world-wide, were analyzed, a high genetic diversity (with 88% of alleles) being observed in accordance with other virulence factors. The phylogenetic analysis did not reveal the separation of strains per geographical region according to a bacterial panmictic population. When compared to other genes of virulence factors of H. pylori, such as the vacuolating cytotoxin A (vacA), nap presents slightly lower genetic variability, concerning the number of alleles and polymorphic sites, pointing to a possible lower pressure of the host immune system. The nap genetic diversity is associated to a high proportion of synonymous substitutions in relation to non-synonymous substitutions, pointing to equilibrium between the need for antigenic diversity as a mechanism to escape the host immune system and the maintenance of the proteins function. All this information could be put to good use when planning the NAP application as a therapeutic or diagnostic target.

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