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 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 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 Fungal Extracellular Vesicles as Potential Targets for Immune Interventions

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Mateus Silveira Freitas ◽  
Vânia Luiza Deperon Bonato ◽  
Andre Moreira Pessoni ◽  
Marcio L. Rodrigues ◽  
Arturo Casadevall ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Nucleic Acids ◽  
Extracellular Vesicles ◽  
Fungal Pathogen ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Therapeutic Strategies ◽  
Host Immune System ◽  
Immunomodulatory Properties

ABSTRACT The release of extracellular vesicles (EVs) by fungi is a fundamental cellular process. EVs carry several biomolecules, including pigments, proteins, enzymes, lipids, nucleic acids, and carbohydrates, and are involved in physiological and pathological processes. EVs may play a pivotal role in the establishment of fungal infections, as they can interact with the host immune system to elicit multiple outcomes. It has been observed that, depending on the fungal pathogen, EVs can exacerbate or attenuate fungal infections. The study of the interaction between fungal EVs and the host immune system and understanding of the mechanisms that regulate those interactions might be useful for the development of new adjuvants as well as the improvement of protective immune responses against infectious or noninfectious diseases. In this review, we describe the immunomodulatory properties of EVs produced by pathogenic fungi and discuss their potential as adjuvants for prophylactic or therapeutic strategies.

Pathogen recognition in the innate immune response

2009 ◽  
Vol 420 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Himanshu Kumar ◽  
Taro Kawai ◽  
Shizuo Akira
Keyword(s):  
Immune Responses ◽  
Germ Line ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Signalling Pathways ◽  
Pathogen Recognition ◽  
Adaptive Immune ◽  
Evolutionarily Conserved ◽  
Cellular Compartments ◽  
Inducible Gene

Immunity against microbial pathogens primarily depends on the recognition of pathogen components by innate receptors expressed on immune and non-immune cells. Innate receptors are evolutionarily conserved germ-line-encoded proteins and include TLRs (Toll-like receptors), RLRs [RIG-I (retinoic acid-inducible gene-I)-like receptors] and NLRs (Nod-like receptors). These receptors recognize pathogens or pathogen-derived products in different cellular compartments, such as the plasma membrane, the endosomes or the cytoplasm, and induce the expression of cytokines, chemokines and co-stimulatory molecules to eliminate pathogens and instruct pathogen-specific adaptive immune responses. In the present review, we will discuss the recent progress in the study of pathogen recognition by TLRs, RLRs and NLRs and their signalling pathways.

scholarly journals Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Visesato Mor ◽  
Antonella Rella ◽  
Amir M. Farnoud ◽  
Ashutosh Singh ◽  
Mansa Munshi ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Sequencing Analysis ◽  
Fungal Cell ◽  
New Class ◽  
Narrow Spectrum

ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. IMPORTANCE Fungal infections are a significant cause of morbidity and mortality worldwide. Current antifungal drugs suffer from various drawbacks, including toxicity, drug resistance, and narrow spectrum of activity. In this study, we have demonstrated that pharmaceutical inhibition of fungal glucosylceramide presents a new opportunity to treat cryptococcosis and various other fungal infections. In addition to being effective against pathogenic fungi, the compounds discovered in this study were well tolerated by animals and additive to current antifungals. These findings suggest that these drugs might pave the way for the development of a new class of antifungals.

scholarly journals The Many Roles of Galectin-3, a Multifaceted Molecule, in Innate Immune Responses against Pathogens

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Laura Díaz-Alvarez ◽  
Enrique Ortega
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Terminal Protein ◽  
Molecular Pattern ◽  
Evolutionarily Conserved ◽  
Carbohydrate Recognition Domains ◽  
Galectin 3 ◽  
The Many ◽  
Recognition Receptor

Galectins are a group of evolutionarily conserved proteins with the ability to bindβ-galactosides through characteristic carbohydrate-recognition domains (CRD). Galectin-3 is structurally unique among all galectins as it contains a C-terminal CRD linked to an N-terminal protein-binding domain, being the only chimeric galectin. Galectin-3 participates in many functions, both intra- and extracellularly. Among them, a prominent role for Galectin-3 in inflammation has been recognized. Galectin-3 has also been shown to directly bind to pathogens and to have various effects on the functions of the cells of the innate immune system. Thanks to these two properties, Galectin-3 participates in several ways in the innate immune response against invading pathogens. Galectin-3 has been proposed to function not only as a pattern-recognition receptor (PRR) but also as a danger-associated molecular pattern (DAMP). In this review, we analyze the various roles that have been assigned to Galectin-3, both as a PRR and as a DAMP, in the context of immune responses against pathogenic microorganisms.

scholarly journals Production of Eicosanoids and Other Oxylipins by Pathogenic Eukaryotic Microbes

2003 ◽  
Vol 16 (3) ◽  
pp. 517-533 ◽  
Author(s):  
Mairi C. Noverr ◽  
John R. Erb-Downward ◽  
Gary B. Huffnagle
Keyword(s):  
Immune Responses ◽  
Pathogenic Fungi ◽  
Host Cells ◽  
Chemokine Production ◽  
Host Immune Responses ◽  
Potential Link ◽  
Leukocyte Chemotaxis ◽  
Eukaryotic Microbes ◽  
Precise Role

SUMMARY Oxylipins are oxygenated metabolites of fatty acids. Eicosanoids are a subset of oxylipins and include the prostaglandins and leukotrienes, which are potent regulators of host immune responses. Host cells are one source of eicosanoids and oxylipins during infection; however, another potential source of eicosanoids is the pathogen itself. A broad range of pathogenic fungi, protozoa, and helminths produce eicosanoids and other oxylipins by novel synthesis pathways. Why do these organisms produce oxylipins? Accumulating data suggest that phase change and differentiation in these organisms are controlled by oxylipins, including prostaglandins and lipoxygenase products. The precise role of pathogen-derived eicosanoids in pathogenesis remains to be determined, but the potential link between pathogen eicosanoids and the development of TH2 responses in the host is intriguing. Mammalian prostaglandins and leukotrienes have been studied extensively, and these molecules can modulate Th1 versus Th2 immune responses, chemokine production, phagocytosis, lymphocyte proliferation, and leukocyte chemotaxis. Thus, eicosanoids and oxylipins (host or microbe) may be mediators of a direct host-pathogen “cross-talk” that promotes chronic infection and hypersensitivity disease, common features of infection by eukaryotic pathogens.

scholarly journals Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

2016 ◽  
Vol 90 (8) ◽  
pp. 3810-3818 ◽  
Author(s):  
Bjoern Meyer ◽  
Hinh Ly
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Multiorgan Failure ◽  
Hemorrhagic Fever ◽  
Innate Immune ◽  
Lassa Virus ◽  
Immune Recognition ◽  
African Countries ◽  
Host Immune Responses

Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.

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.

Sign in / Sign up

Export Citation Format

Share Document