scholarly journals Chlamydia and Its Many Ways of Escaping the Host Immune System

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Won Fen Wong ◽  
James P. Chambers ◽  
Rishein Gupta ◽  
Bernard P. Arulanandam
Keyword(s):  
Immune Responses ◽  
Host Cell ◽  
Acid Synthesis ◽  
Host Immune System ◽  
Amino Acid Synthesis ◽  
Future Studies ◽  
Host Immune Responses ◽  
Host Cell Apoptosis ◽  
Host Cell Death ◽  
Intracytoplasmic Inclusions

The increasing number of new cases of Chlamydia infection worldwide may be attributed to the pathogen’s ability to evade various host immune responses. Summarized here are means of evasion utilized by Chlamydia enabling survival in a hostile host environment. The pathogen's persistence involves a myriad of molecular interactions manifested in a variety of ways, e.g., formation of membranous intracytoplasmic inclusions and cytokine-induced amino acid synthesis, paralysis of phagocytic neutrophils, evasion of phagocytosis, inhibition of host cell apoptosis, suppression of antigen presentation, and induced expression of a check point inhibitor of programmed host cell death. Future studies could focus on the targeting of these molecules associated with immune evasion, thus limiting the spread and tissue damage caused by this pathogen.

scholarly journals Genetic Screen inChlamydia muridarumReveals Role for an Interferon-Induced Host Cell Death Program in Antimicrobial Inclusion Rupture

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Amanda M. Giebel ◽  
Shuai Hu ◽  
Krithika Rajaram ◽  
Ryan Finethy ◽  
Evelyn Toh ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Host Cell ◽  
Host Defense ◽  
Genetic Screen ◽  
Content Type ◽  
Host Immune Responses ◽  
Interferon Stimulated Genes ◽  
Host Cell Death ◽  
Ifn Γ

ABSTRACTInterferon-regulated immune defenses protect mammals from pathogenically diverse obligate intracellular bacterial pathogens of the genusChlamydia. Interferon gamma (IFN-γ) is especially important in controlling the virulence ofChlamydiaspecies and thus impacts the modeling of human chlamydial infection and disease in mice. How IFN-γ contributes to cell-autonomous defenses againstChlamydiaspecies and how these pathogens evade IFN-γ-mediated immunity in their natural hosts are not well understood. We conducted a genetic screen which identified 31IFN-γ-sensitive (Igs) mutants of the mouse model pathogenChlamydia muridarum. Genetic suppressor analysis and lateral gene transfer were used to map the phenotype of one of these mutants, Igs4, to a missense mutation in a putative chlamydial inclusion membrane protein, TC0574. We observed the lytic destruction of Igs4-occupied inclusions and accompanying host cell death in response to IFN-γ priming or various proapoptotic stimuli. However, Igs4 was insensitive to IFN-γ-regulated cell-autonomous defenses previously implicated in anti-Chlamydia trachomatishost defense in mice. Igs4 inclusion integrity was restored by caspase inhibitors, indicating that the IFN-γ-mediated destruction of Igs4 inclusions is dependent upon the function of caspases or related prodeath cysteine proteases. We further demonstrated that the Igs4 mutant is immune restricted in an IFN-γ-dependent manner in a mouse infection model, thereby implicating IFN-γ-mediated inclusion destruction and host cell death as potentin vivohost defense mechanisms to which wild-typeC. muridarumis resistant. Overall, our results suggest thatC. muridarumevolved resistance mechanisms to counter IFN-γ-elicited programmed cell death and the associated destruction of intravacuolar pathogens.IMPORTANCEMultiple obligatory intracellular bacteria in the genusChlamydiaare important pathogens. In humans, strains ofC. trachomatiscause trachoma, chlamydia, and lymphogranuloma venereum. These diseases are all associated with extended courses of infection and reinfection that likely reflect the ability of chlamydiae to evade various aspects of host immune responses. Interferon-stimulated genes, driven in part by the cytokine interferon gamma, restrict the host range of variousChlamydiaspecies, but how these pathogens evade interferon-stimulated genes in their definitive host is poorly understood. VariousChlamydiaspecies can inhibit death of their host cells and may have evolved this strategy to evade prodeath signals elicited by host immune responses. We present evidence that chlamydia-induced programmed cell death resistance evolved to counter interferon- and immune-mediated killing ofChlamydia-infected cells.

scholarly journals TolC-Dependent Modulation of Host Cell Death by the Francisella tularensis Live Vaccine Strain

2014 ◽  
Vol 82 (5) ◽  
pp. 2068-2078 ◽  
Author(s):  
Christopher R. Doyle ◽  
Ji-An Pan ◽  
Patricio Mena ◽  
Wei-Xing Zong ◽  
David G. Thanassi
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Host Cell ◽  
Francisella Tularensis ◽  
Vaccine Strain ◽  
Live Vaccine ◽  
Live Vaccine Strain ◽  
Type I ◽  
Content Type ◽  
Host Cell Death

ABSTRACTFrancisella tularensisis a facultative intracellular, Gram-negative pathogen and the causative agent of tularemia. We previously identified TolC as a virulence factor of theF. tularensislive vaccine strain (LVS) and demonstrated that a ΔtolCmutant exhibits increased cytotoxicity toward host cells and elicits increased proinflammatory responses compared to those of the wild-type (WT) strain. TolC is the outer membrane channel component used by the type I secretion pathway to export toxins and other bacterial virulence factors. Here, we show that the LVS delays activation of the intrinsic apoptotic pathway in a TolC-dependent manner, both during infection of primary macrophages and during organ colonization in mice. The TolC-dependent delay in host cell death is required forF. tularensisto preserve its intracellular replicative niche. We demonstrate that TolC-mediated inhibition of apoptosis is an active process and not due to defects in the structural integrity of the ΔtolCmutant. These findings support a model wherein the immunomodulatory capacity ofF. tularensisrelies, at least in part, on TolC-secreted effectors. Finally, mice vaccinated with the ΔtolCLVS are protected from lethal challenge and clear challenge doses faster than WT-vaccinated mice, demonstrating that the altered host responses to primary infection with the ΔtolCmutant led to altered adaptive immune responses. Taken together, our data demonstrate that TolC is required for temporal modulation of host cell death during infection byF. tularensisand highlight how shifts in the magnitude and timing of host innate immune responses may lead to dramatic changes in the outcome of infection.

scholarly journals Protective and Pathogenic Immune Responses to Cutaneous Leishmaniasis

2021 ◽  
Author(s):  
Elina Panahi ◽  
Danielle I. Stanisic ◽  
Christopher S. Peacock ◽  
Lara J. Herrero
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cutaneous Leishmaniasis ◽  
Adaptive Immune Response ◽  
Leishmania Parasite ◽  
Host Immune System ◽  
Phagocytic Cells ◽  
Host Immune Responses ◽  
Outcome Severity ◽  
Common Clinical Presentation

Leishmania (Kinetoplastida: Trypanosomatidae) parasites are known to cause a broad spectrum of clinical diseases in humans, collectively known as the leishmaniases. Cutaneous leishmaniasis is the most common clinical presentation with varying degrees of severity largely driven by host immune responses, specifically the interplay between innate and adaptive immune response. The establishment of a T lymphocyte driven cell-mediated immune response, leading to activated phagocytic cells, leading to Leishmania parasite killing and control of infection. Alternatively, the Leishmania parasite manipulates the host immune system, enabling parasite proliferation and clinical disease. Here we review how the cumulative interactions of different aspects of the host immune response determines disease outcome, severity, and immunity to re-infection.

An appraisal of survival strategies

Parasitology ◽  
1984 ◽  
Vol 88 (4) ◽  
pp. 575-577 ◽  
Author(s):  
N. A. Mitchison
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Survival Strategies ◽  
Host Immune System ◽  
Cellular Immunology ◽  
Host Immune Responses ◽  
Host Defence System ◽  
Bio Engineering

Only a few years ago parasite immunology looked an unattractive subject better left to the dogged specialists. Parasites and hosts had been playing chess together for a million years, and there seemed little prospect of perturbing matters in favour of the host immune system. All that has changed, for three reasons. Firstly, we have learned how to grow at least some parasites in vitro, and prospects of doing so with others are encouraging. Secondly, progress in cellular immunology has revealed the sort of loopholes in the host defence system which parasites are likely to exploit: we are learning the questions which matter about parasites as antigens. Thirdly, and most importantly, molecular genetics is being brought to bear on parasites: we can now see a real, though long-term, prospect of manufacturing practicable vaccines through bio-engineering, and more immediately it gives us the tools needed to probe the host immune responses in the form of cloned antigens.

Leishmanial selenoproteins and the host immune system: towards new therapeutic strategies?

2020 ◽  
Vol 114 (7) ◽  
pp. 541-544
Author(s):  
Sajad Rashidi ◽  
Kurosh Kalantar ◽  
Paul Nguewa ◽  
Gholamreza Hatam
Keyword(s):  
Immune System ◽  
Adverse Effects ◽  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Strategies ◽  
Host Immune System ◽  
Host Immune Responses ◽  
Leishmania Parasites

Abstract Optimum levels of selenoproteins are essential for starting and managing the host immune responses against pathogens. According to the expression of selenoproteins in Leishmania parasites, and since high levels of selenoproteins lead to adverse effects on immune cells and their functions, Leishmania parasites might then express selenoproteins such as selenomethionine in their structure and/or secretions able to challenge the host immune system. Finally, this adaptation may lead to evasion of the parasite from the host immune system. The expression of selenoproteins in Leishmania parasites might then induce the development of infection. We therefore suggest these molecules as new therapeutic candidates for the treatment of leishmaniasis.

scholarly journals Evolution of animal immunity in the light of beneficial symbioses

2020 ◽  
Vol 375 (1808) ◽  
pp. 20190601 ◽  
Author(s):  
Nicole M. Gerardo ◽  
Kim L. Hoang ◽  
Kayla S. Stoy
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Host Immune System ◽  
System Evolution ◽  
Symbiotic Associations ◽  
Host Immune Responses ◽  
Immune System Evolution ◽  
System Maintenance ◽  
Key Aspects ◽  
Host Evolution

Immune system processes serve as the backbone of animal defences against pathogens and thus have evolved under strong selection and coevolutionary dynamics. Most microorganisms that animals encounter, however, are not harmful, and many are actually beneficial. Selection should act on hosts to maintain these associations while preventing exploitation of within-host resources. Here, we consider how several key aspects of beneficial symbiotic associations may shape host immune system evolution. When host immunity is used to regulate symbiont populations, there should be selection to evolve and maintain targeted immune responses that recognize symbionts and suppress but not eliminate symbiont populations. Associating with protective symbionts could relax selection on the maintenance of redundant host-derived immune responses. Alternatively, symbionts could facilitate the evolution of host immune responses if symbiont-conferred protection allows for persistence of host populations that can then adapt. The trajectory of immune system evolution will likely differ based on the type of immunity involved, the symbiont transmission mode and the costs and benefits of immune system function. Overall, the expected influence of beneficial symbiosis on immunity evolution depends on how the host immune system interacts with symbionts, with some interactions leading to constraints while others possibly relax selection on immune system maintenance. This article is part of the theme issue ‘The role of the microbiome in host evolution’.

Here’s the TIP (Tri-Immuno – Phasic periodontal therapy) – A dive to thrive!

2021 ◽  
Vol 13 (4) ◽  
pp. 288-292
Author(s):  
Kahon Chakraborty ◽  
Sachin S Shivanaikar ◽  
Darsha Jain
Keyword(s):  
Immune Responses ◽  
Alveolar Bone ◽  
Periodontal Diseases ◽  
Chronic Inflammatory Disease ◽  
Host Immune System ◽  
Alternative Technique ◽  
Lifestyle Modifications ◽  
Host Immune Responses ◽  
Periodontal Tissues ◽  
The Past

Periodontitis is a multifactorial chronic inflammatory disease of the periodontium that destroys periodontium due to the exaggeration of the host immune responses to the disease-causing perio-pathogens, resulting in attachment loss and bone loss, eventually leading to loss of the tooth. Various advancements in modalities of treatment of periodontal disease have occurred in the past few years to overcome the disadvantages of traditional periodontal therapies as well as to improve the clinical outcomes. The Tri-Immuno – phasic periodontal (TIP) therapy is one such new technique developed by William Hoisington which is a minimally invasive, efficient, safe, and less traumatic alternative technique for treating periodontal diseases. TIP therapy is based on the fact that periodontal tissues heal in the same way as other parts of the human body. TIP therapy is an aerobic method of treating periodontal diseases that modulates various phases of the host immune system to eliminate the perio-pathogens and form a new attachment, and also attempts to regenerate the alveolar bone. The TIP therapy method includes - Bone One Session Treatment (BOST), controlling the occlusal forces, oral hygiene reinforcement with adjuvant modalities, lifestyle modifications, enhancing nutrition, and exercise.

scholarly journals Nitrogen sourcing during viral infection of marine cyanobacteria

2019 ◽  
Vol 116 (31) ◽  
pp. 15590-15595 ◽  
Author(s):  
Jacob R. Waldbauer ◽  
Maureen L. Coleman ◽  
Adriana I. Rizzo ◽  
Kathryn L. Campbell ◽  
John Lotus ◽  
...  
Keyword(s):  
Host Cell ◽  
Isotope Labeling ◽  
De Novo ◽  
Building Blocks ◽  
Acid Synthesis ◽  
Host Protein ◽  
Dependent Manner ◽  
Host Proteins ◽  
Amino Acid Synthesis ◽  
Progeny Phage

The building blocks of a virus derived from de novo biosynthesis during infection and/or catabolism of preexisting host cell biomass, and the relative contribution of these 2 sources has important consequences for understanding viral biogeochemistry. We determined the uptake of extracellular nitrogen (N) and its biosynthetic incorporation into both virus and host proteins using an isotope-labeling proteomics approach in a model marine cyanobacterium Synechococcus WH8102 infected by a lytic cyanophage S-SM1. By supplying dissolved N as 15N postinfection, we found that proteins in progeny phage particles were composed of up to 41% extracellularly derived N, while proteins of the infected host cell showed almost no isotope incorporation, demonstrating that de novo amino acid synthesis continues during infection and contributes specifically and substantially to phage replication. The source of N for phage protein synthesis shifted over the course of infection from mostly host derived in the early stages to more medium derived later on. We show that the photosystem II reaction center proteins D1 and D2, which are auxiliary metabolic genes (AMGs) in the S-SM1 genome, are made de novo during infection in an apparently light-dependent manner. We also identified a small set of host proteins that continue to be produced during infection; the majority are homologs of AMGs in S-SM1 or other viruses, suggesting selective continuation of host protein production during infection. The continued acquisition of nutrients by the infected cell and their utilization for phage replication are significant for both evolution and biogeochemical impact of viruses.

scholarly journals A tolC Mutant of Francisella tularensis Is Hypercytotoxic Compared to the Wild Type and Elicits Increased Proinflammatory Responses from Host Cells

2009 ◽  
Vol 78 (3) ◽  
pp. 1022-1031 ◽  
Author(s):  
Gabrielle J. Platz ◽  
DeAnna C. Bublitz ◽  
Patricio Mena ◽  
Jorge L. Benach ◽  
Martha B. Furie ◽  
...  
Keyword(s):  
Cell Death ◽  
Host Cell ◽  
Francisella Tularensis ◽  
Host Cells ◽  
Type I ◽  
Wild Type ◽  
Human Macrophages ◽  
Host Immune Responses ◽  
Host Cell Death ◽  
Proinflammatory Responses

ABSTRACT The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen and the causative agent of tularemia. TolC, which is an outer membrane protein involved in drug efflux and type I protein secretion, is required for the virulence of the F. tularensis live vaccine strain (LVS) in mice. Here, we show that an LVS ΔtolC mutant colonizes livers, spleens, and lungs of mice infected intradermally or intranasally, but it is present at lower numbers in these organs than in those infected with the parental LVS. For both routes of infection, colonization by the ΔtolC mutant is most severely affected in the lungs, suggesting that TolC function is particularly important in this organ. The ΔtolC mutant is hypercytotoxic to murine and human macrophages compared to the wild-type LVS, and it elicits the increased secretion of proinflammatory chemokines from human macrophages and endothelial cells. Taken together, these data suggest that TolC function is required for F. tularensis to inhibit host cell death and dampen host immune responses. We propose that, in the absence of TolC, F. tularensis induces excessive host cell death, causing the bacterium to lose its intracellular replicative niche. This results in lower bacterial numbers, which then are cleared by the increased innate immune response of the host.

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