scholarly journals Recent advances in understanding inherited deficiencies in immunity to infections

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 243 ◽  
Author(s):  
Gregory M. Constantine ◽  
Michail S. Lionakis
Keyword(s):  
Immune Responses ◽  
Host Defense ◽  
Fungal Infections ◽  
Microbial Pathogens ◽  
Host Immune Responses ◽  
Vaccination Strategies ◽  
The World ◽  
Human Immunity ◽  
Immune Pathways ◽  
Resistance To Infection

The immune system is central to our interactions with the world in which we live and importantly dictates our response to potential allergens, toxins, and pathogens to which we are constantly exposed. Understanding the mechanisms that underlie protective host immune responses against microbial pathogens is vital for the development of improved treatment and vaccination strategies against infections. To that end, inherited immunodeficiencies that manifest with susceptibility to bacterial, viral, and/or fungal infections have provided fundamental insights into the indispensable contribution of key immune pathways in host defense against various pathogens. In this mini-review, we summarize the findings from a series of recent publications in which inherited immunodeficiencies have helped illuminate the interplay of human immunity and resistance to infection.

scholarly journals Emerging Roles of Protein Deamidation in Innate Immune Signaling

2016 ◽  
Vol 90 (9) ◽  
pp. 4262-4268 ◽  
Author(s):  
Jun Zhao ◽  
Junhua Li ◽  
Simin Xu ◽  
Pinghui Feng
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Biological Processes ◽  
Innate Immune Responses ◽  
Immune Signaling ◽  
Host Immune Responses ◽  
Innate Immune Signaling ◽  
Enzyme Deficient ◽  
Signaling Components

Protein deamidation has been considered a nonenzymatic process associated with protein functional decay or “aging.” Recent studies implicate protein deamidation in regulating signal transduction in fundamental biological processes, such as innate immune responses. Work investigating gammaherpesviruses and bacterial pathogens indicates that microbial pathogens deploy deamidases or enzyme-deficient homologues (pseudoenzymes) to induce deamidation of key signaling components and evade host immune responses. Here, we review studies on protein deamidation in innate immune signaling and present several imminent questions concerning the roles of protein deamidation in infection and immunity.

scholarly journals Analysis of Tuberculosis Meningitis Pathogenesis, Diagnosis, and Treatment

2020 ◽  
Vol 9 (9) ◽  
pp. 2962
Author(s):  
Aysha Arshad ◽  
Sujay Dayal ◽  
Raj Gadhe ◽  
Ajinkya Mawley ◽  
Kevin Shin ◽  
...  
Keyword(s):  
Immune Responses ◽  
Initial Phase ◽  
Multidrug Resistant ◽  
Personality Change ◽  
Diagnosis And Treatment ◽  
Host Immune Responses ◽  
Common Presentation ◽  
Neurological Morbidity ◽  
The World ◽  
Resistant Strains

Tuberculosis (TB) is the most prevalent infectious disease in the world. In recent years there has been a significant increase in the incidence of TB due to the emergence of multidrug resistant strains of Mycobacterium tuberculosis (M. tuberculosis) and the increased numbers of highly susceptible immuno-compromised individuals. Central nervous system TB, includes TB meningitis (TBM-the most common presentation), intracranial tuberculomas, and spinal tuberculous arachnoiditis. Individuals with TBM have an initial phase of malaise, headache, fever, or personality change, followed by protracted headache, stroke, meningismus, vomiting, confusion, and focal neurologic findings in two to three weeks. If untreated, mental status deteriorates into stupor or coma. Delay in the treatment of TBM results in, either death or substantial neurological morbidity. This review provides latest developments in the biomedical research on TB meningitis mainly in the areas of host immune responses, pathogenesis, diagnosis, and treatment of this disease.

scholarly journals Diagnosis and treatment of invasive Candida infections – a review article

2019 ◽  
Vol 73 (1) ◽  
pp. 47
Author(s):  
Marta Dąbrowska ◽  
Monika Sienkiewicz ◽  
Paweł Kwiatkowski ◽  
Michał Dąbrowski
Keyword(s):  
Immune Responses ◽  
Fungal Infections ◽  
Review Article ◽  
Source Control ◽  
Candida Spp ◽  
Common Cause ◽  
Host Immune Responses ◽  
Invasive Infections ◽  
Candida Infections ◽  
Short Time

<p>Candida albicans is the most common cause of fungal infections worldwide. Invasive candidiasis comprises candidemia and deep-seated candidiasis. Most yeast invasive infections are endogenous with a high mortality. Pathogenesis of candidiasis depends on avoiding host immune responses, as well as the virulence factors of the fungus enabling colonization and invasion of tissues. Adequate source control and antifungal therapy administered within a short time is critical to get a better prognosis. The emergence of drug resistance and the side effects of currently available antifungals are becoming the major problem in the management of Candida spp. infection.</p>

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 Chitin, Chitinase Responses, and Invasive Fungal Infections

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Karina Vega ◽  
Markus Kalkum
Keyword(s):  
Immune Responses ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Therapeutic Approaches ◽  
Human Immune System ◽  
Cell Wall Component ◽  
Diagnostic Assays ◽  
Host Immune Responses ◽  
Human Immune ◽  
Novel Therapeutic

The human immune system is capable of recognizing and degrading chitin, an important cell wall component of pathogenic fungi. In the context of host-immune responses to fungal infections, herein we review the particular contributions and interplay of fungus and chitin recognition, and chitin-degrading enzymes, known as chitinases. The mechanisms of host chitinase responses may have implications for diagnostic assays as well as novel therapeutic approaches for patients that are at risk of contracting fatal fungal infections.

scholarly journals Modulating host immune responses to fight invasive fungal infections

2017 ◽  
Vol 40 ◽  
pp. 95-103 ◽  
Author(s):  
James E Scriven ◽  
Mark W Tenforde ◽  
Stuart M Levitz ◽  
Joseph N Jarvis
Keyword(s):  
Immune Responses ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Host Immune Responses

scholarly journals Candidalysin: From Mechanism of Action to Biomarker Development and Therapeutic Response

2020 ◽  
Author(s):  
Yao-Qi Chen ◽  
Qian Li ◽  
Tian-Yi Zhang ◽  
Ning-Ning Liu
Keyword(s):  
Host Defense ◽  
Fungal Pathogens ◽  
Therapeutic Response ◽  
Fungal Infections ◽  
Specific Gene ◽  
Clinical Settings ◽  
Diagnostic Biomarker ◽  
Systemic Fungal Infection ◽  
The World ◽  
Peptide Toxin

ABSTRACT The incidence of systemic fungal infection is increasing, and millions of people around the world suffer from fungal infections. Candida albicans is one of the most frequently isolated fungal pathogens in clinical settings. As a polymorphic organism, the transition between yeast and hyphae is critical for C. albicans virulence and pathogenesis. However, the mechanism of hyphae-associated virulence remains unclear. Candidalysin is the first human fungal cytolytic peptide toxin originating from the hyphae-specific gene, ECE1. This review will summarize the most recent progress underlying candidalysin-mediated epithelial damage and host defense pathways, which might shed new light on the development of a novel antifungal strategy and early diagnostic biomarker.

scholarly journals Regulated Cell Death as a Therapeutic Target for Novel Antifungal Peptides and Biologics

2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Michael R. Yeaman ◽  
Sabrina Büttner ◽  
Karin Thevissen
Keyword(s):  
Cell Death ◽  
Host Defense ◽  
Fungal Infections ◽  
Fungal Resistance ◽  
Microbial Pathogens ◽  
Severe Illness ◽  
Global Public Health ◽  
Host Defense Peptides ◽  
Regulated Cell Death ◽  
Drug Actions

The rise of microbial pathogens refractory to conventional antibiotics represents one of the most urgent and global public health concerns for the 21st century. Emergence of Candida auris isolates and the persistence of invasive mold infections that resist existing treatment and cause severe illness has underscored the threat of drug-resistant fungal infections. To meet these growing challenges, mechanistically novel agents and strategies are needed that surpass the conventional fungistatic or fungicidal drug actions. Host defense peptides have long been misunderstood as indiscriminant membrane detergents. However, evidence gathered over the past decade clearly points to their sophisticated and selective mechanisms of action, including exploiting regulated cell death pathways of their target pathogens. Such peptides perturb transmembrane potential and mitochondrial energetics, inducing phosphatidylserine accessibility and metacaspase activation in fungi. These mechanisms are often multimodal, affording target pathogens fewer resistance options as compared to traditional small molecule drugs. Here, recent advances in the field are examined regarding regulated cell death subroutines as potential therapeutic targets for innovative anti-infective peptides against pathogenic fungi. Furthering knowledge of protective host defense peptide interactions with target pathogens is key to advancing and applying novel prophylactic and therapeutic countermeasures to fungal resistance and pathogenesis.

scholarly journals An Invertebrate Host to Study Fungal Infections, Mycotoxins and Antifungal Drugs: Tenebrio molitor

2018 ◽  
Vol 4 (4) ◽  
pp. 125 ◽  
Author(s):  
Patrícia Canteri de Souza ◽  
Carla Custódio Caloni ◽  
Duncan Wilson ◽  
Ricardo Sergio Almeida
Keyword(s):  
Immune Responses ◽  
Potential Model ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Tenebrio Molitor ◽  
Antifungal Drugs ◽  
Innate Immune ◽  
Fungal Virulence ◽  
Host Immune Responses ◽  
Evolutionarily Conserved

Faced with ethical conflict and social pressure, researchers have increasingly chosen to use alternative models over vertebrates in their research. Since the innate immune system is evolutionarily conserved in insects, the use of these animals in research is gaining ground. This review discusses Tenebrio molitor as a potential model host for the study of pathogenic fungi. Larvae of T. molitor are known as cereal pests and, in addition, are widely used as animal and human feed. A number of studies on mechanisms of the humoral system, especially in the synthesis of antimicrobial peptides, which have similar characteristics to vertebrates, have been performed. These studies demonstrate the potential of T. molitor larvae as a model host that can be used to study fungal virulence, mycotoxin effects, host immune responses to fungal infection, and the action of antifungal compounds.

scholarly journals Hyperinflammation Syndrome in COVID-19 Disease: Pathogenesis and Potential Immunomodulatory Agents

2021 ◽  
Author(s):  
Moulid Hidayat ◽  
Diah Handayani ◽  
Fariz Nurwidya ◽  
Sita Laksmi Andarini
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Distress Syndrome ◽  
Multiorgan Failure ◽  
Immunosuppressive Agents ◽  
Clinical Manifestations ◽  
Disease Pathogenesis ◽  
Immunomodulatory Agents ◽  
Host Immune Responses ◽  
The World

The coronavirus disease 2019 (COVID-19) pandemic caused by infection of the SARS-CoV-2 virus has affected millions of people in the world. The pathogenesis and clinical manifestations of COVID-19 disease are tightly influenced by the host immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In some condition, the immune response might be uncontrolled, giving rise to hyperinflammatory conditions marked by excessive release of proinflammatory cytokines (cytokine storms) in severe COVID-19 patients, which then can cause acute respiratory distress syndrome (ARDS), multiorgan failure, and death. Furthermore, treatment using immunomodulator agents including immunostimulatory and immunosuppressive agents can be an option in achieving successful treatment. In this review, we discuss the pathogenesis of the disease, including host immune responses to SARS-CoV-2 virus infection, and immune mechanisms which contribute to the disease severity and death as well as several potential immunomodulatory agents which can be used in the management of hyperinflammatory syndrome of severe COVID-19.

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