scholarly journals Do Mast Cells Contribute to the Antifungal Host Defense?

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2510
Author(s):  
Paulina Żelechowska ◽  
Joanna Pastwińska ◽  
Ewa Brzezińska-Błaszczyk ◽  
Justyna Agier
Keyword(s):  
Mast Cells ◽  
Host Defense ◽  
Immune Cells ◽  
Defense Mechanisms ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Extracellular Dna ◽  
Opportunistic Pathogens ◽  
Strategic Location ◽  
Fungal Kingdom

The fungal kingdom includes a group of microorganisms that are widely distributed in the environment, and therefore the exposure to them is almost constant. Furthermore, fungal components of the microbiome, i.e., mycobiome, could serve as a reservoir of potentially opportunistic pathogens. Despite close encounters with fungi, defense mechanisms that develop during fungal infections remain unexplored. The strategic location of mast cells (MCs) close to the external environment places them among the first cells to encounter pathogens along with the other innate immune cells. MCs are directly involved in the host defense through the ability to destroy pathogens or indirectly by activating other immune cells. Most available data present MCs’ involvement in antibacterial, antiviral, or antiparasitic defense mechanisms. However, less is known about their contribution in defense mechanisms against fungi. MCs may support immune responses to fungi or their specific molecules through initiated degranulation, synthesis and release of cytokines, chemokines, mediators, and generation of reactive oxygen species (ROS), as well as immune cells’ recruitment, phagocytosis, or provision of extracellular DNA traps. This review summarizes current knowledge on host defense mechanisms against fungi and MCs’ involvement in those processes. It also describes the effects of fungi or fungus-derived constituents on MCs’ activity.

scholarly journals Roles of a Mast Cell–Specific Receptor MRGPRX2 in Host Defense and Inflammation

2020 ◽  
Vol 99 (8) ◽  
pp. 882-890 ◽  
Author(s):  
C. Chompunud Na Ayudhya ◽  
S. Roy ◽  
M. Thapaliya ◽  
H. Ali
Keyword(s):  
Mast Cells ◽  
Bacterial Infection ◽  
Host Defense ◽  
Immune Cells ◽  
Inflammatory Pain ◽  
Bacterial Infections ◽  
Neurogenic Inflammation ◽  
Inflammatory Diseases ◽  
Adaptive Immune Cells ◽  
Novel Approaches

Mast cells are multifunctional immune cells that are found most abundantly at host-environment interfaces, such as the skin, respiratory tract, and oral/gastrointestinal mucosa. Not surprisingly, mast cells act as sentinel cells that sense microbial attacks and initiate a protective immune response and promote healing. Although mast cells share many features with other innate immune effector cells, such as neutrophils and macrophages, they uniquely interact closely with blood vessels and release an extensive set of mediators for the recruitment of innate and adaptive immune cells. A novel human G protein-coupled receptor (GPCR), known as Mas-related GPCR-X2 (MRGPRX2, mouse ortholog, MrgprB2), has recently been identified, which is expressed on mast cells but not neutrophils and macrophages. Interestingly, activation of MrgprB2 by bacteria-derived quorum-sensing peptides inhibits bacterial growth, prevents biofilm formation, and leads to the recruitment of neutrophils to effectively clear bacteria. Furthermore, host defense antimicrobial peptides and small-molecule peptide mimetics also activate mast cells via MRGPRX2/B2. MrgprB2-mediated activation of local mast cells also clears cutaneous bacterial infection, promotes healing, and protects against reinfection. In addition to their role in host defense, mast cells contribute to a number of chronic inflammatory diseases such as periodontitis, neurogenic inflammation, and inflammatory pain likely via the activation of MRGPRX2. In this review, we discuss the roles of MRGPRX2/B2 in the clearance of bacterial infection, wound healing, periodontal disease, neurogenic inflammation, and inflammatory pain. We propose that harnessing mast cells’ host defense and immunomodulatory properties via the activation of MRGPRX2 may lead to novel approaches for the treatment of drug-resistant bacterial infections. On the other hand, increased MRGPRX2 expression on mast cells and their inappropriate activation may contribute to periodontitis, neurogenic inflammation, and inflammatory pain. Thus, targeting MRGPRX2 could provide novel approaches to modulate these conditions.

Host Defense Mechanisms and the Superficial Fungal Infections

1984 ◽  
Vol 2 (1) ◽  
pp. 67-79 ◽  
Author(s):  
Terry W. Marsh ◽  
William M. Artis
Keyword(s):  
Host Defense ◽  
Defense Mechanisms ◽  
Fungal Infections

scholarly journals CandidaInfections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Claudia Spampinato ◽  
Darío Leonardi
Keyword(s):  
Antifungal Agents ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Diagnostic Methods ◽  
Opportunistic Pathogens ◽  
Yeast Infection ◽  
Life Threatening ◽  
Therapeutic Alternatives

The genusCandidaincludes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised.Candidainfections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genusCandidaand yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment ofCandidainfections is also provided.

scholarly journals Immunological Aspects ofCandidaandAspergillusSystemic Fungal Infections

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Christoph Mueller-Loebnitz ◽  
Helmut Ostermann ◽  
Anke Franzke ◽  
Juergen Loeffler ◽  
Lutz Uharek ◽  
...  
Keyword(s):  
High Risk ◽  
Defense Mechanisms ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Immunosuppressive Drugs ◽  
Immune Defense ◽  
Immunological Mechanism ◽  
Immune Effector ◽  
Effector Cells ◽  
Risk Patients

Patients with allogeneic stem cell transplantation (SCT) have a high risk of invasive fungal infections (IFIs) even after neutrophil regeneration. Immunological aspects might play a very important role in the IFI development in these patients. Some data are available supporting the identification of high-risk patients with IFI for example patients receiving stem cells from TLR4 haplotype S4 positive donors. Key defense mechanisms against IFI include the activation of neutrophils, the phagocytosis of germinating conidia by dendritic cells, and the fight of the cells of the innate immunity such as monocytes and natural killer cells against germlings and hyphae. Furthermore, immunosuppressive drugs interact with immune effector cells influencing the specific fungal immune defense and antimycotic drugs might interact with immune response. Based on the current knowledge on immunological mechanism inAspergillus fumigatus, the first approaches of an immunotherapy using human T cells are in development. This might be an option for the future of aspergillosis patients having a poor prognosis with conventional treatment.

scholarly journals Involvement of Mast Cells in the Pathophysiology of Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Lijia Mai ◽  
Qing Liu ◽  
Fang Huang ◽  
Hongwen He ◽  
Wenguo Fan
Keyword(s):  
Nervous System ◽  
Mast Cells ◽  
Host Defense ◽  
Immune Cells ◽  
Inflammatory Mediators ◽  
Molecular Mechanisms ◽  
Allergic Diseases ◽  
The Body ◽  
Acquired Immunity ◽  
Effector Cells

Mast cells (MCs) are immune cells and are widely distributed throughout the body. MCs are not only classically viewed as effector cells of some allergic diseases but also participate in host defense, innate and acquired immunity, homeostatic responses, and immunoregulation. Mounting evidence indicates that activation of MCs releasing numerous vasoactive and inflammatory mediators has effects on the nervous system and has been involved in different pain conditions. Here, we review the latest advances made about the implication of MCs in pain. Possible cellular and molecular mechanisms regarding the crosstalk between MC and the nervous system in the initiation and maintenance of pain are also discussed.

scholarly journals Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 461 ◽  
Author(s):  
Ewa Ksiezopolska ◽  
Toni Gabaldón
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Developed Countries ◽  
Antifungal Drugs ◽  
Opportunistic Pathogens ◽  
Evolutionary Mechanisms

Fungal infections, such as candidiasis caused by Candida, pose a problem of growing medical concern. In developed countries, the incidence of Candida infections is increasing due to the higher survival of susceptible populations, such as immunocompromised patients or the elderly. Existing treatment options are limited to few antifungal drug families with efficacies that vary depending on the infecting species. In this context, the emergence and spread of resistant Candida isolates are being increasingly reported. Understanding how resistance can evolve within naturally susceptible species is key to developing novel, more effective treatment strategies. However, in contrast to the situation of antibiotic resistance in bacteria, few studies have focused on the evolutionary mechanisms leading to drug resistance in fungal species. In this review, we will survey and discuss current knowledge on the genetic bases of resistance to antifungal drugs in Candida opportunistic pathogens. We will do so from an evolutionary genomics perspective, focusing on the possible evolutionary paths that may lead to the emergence and selection of the resistant phenotype. Finally, we will discuss the potential of future studies enabled by current developments in sequencing technologies, in vitro evolution approaches, and the analysis of serial clinical isolates.

scholarly journals Current Knowledge on the Biology of Lysophosphatidylserine as an Emerging Bioactive Lipid

2021 ◽  
Author(s):  
Jumpei Omi ◽  
Kuniyuki Kano ◽  
Junken Aoki
Keyword(s):  
Immune System ◽  
Mast Cells ◽  
G Protein ◽  
Lysophosphatidic Acid ◽  
Immune Cells ◽  
Current Knowledge ◽  
G Protein Coupled Receptors ◽  
Sphingosine 1 Phosphate ◽  
Recent Developments ◽  
G Protein Coupled

AbstractLysophosphatidylserine (LysoPS) is an emerging lysophospholipid (LPL) mediator, which acts through G protein-coupled receptors, like lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). LysoPS is detected in various tissues and cells and thought to be produced mainly by the deacylation of phosphatidylserine. LysoPS has been known to stimulate degranulation of mast cells. Recently, four LysoPS-specific G protein-coupled receptors (GPCRs) were identified. These GPCRs belong to the P2Y family which covers receptors for nucleotides and LPLs and are predominantly expressed in immune cells such as lymphocytes and macrophages. Studies on knockout mice of these GPCRs have revealed that LysoPS has immune-modulatory functions. Up-regulation of a LysoPS-producing enzyme, PS-specific phospholipase A1, was frequently observed in situations where the immune system is activated including autoimmune diseases and organ transplantations. Therefore, modulation of LysoPS signaling appears to be a promising method for providing therapies for the treatment of immune diseases. In this review, we summarize the biology of LysoPS-producing enzymes and receptors, recent developments in LysoPS signal modulators, and prospects for future therapeutic applications.

scholarly journals Host Defence to Pulmonary Mycosis

1999 ◽  
Vol 10 (2) ◽  
pp. 147-155 ◽  
Author(s):  
Christopher H Mody ◽  
Peter W Warren
Keyword(s):  
Host Defense ◽  
Defense Mechanisms ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Data Extraction ◽  
Pathogenic Fungi ◽  
Fungal Disease ◽  
Medline Search ◽  
Pulmonary Mycosis ◽  
Immune Defects

OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease.DATA SOURCES: English articles from 1966 to present were identified from a MEDLINE search.STUDY SELECTION: Articles were identified by a MEDLINE search of ‘exp lung/’ or ‘exp lung diseases/’ and ‘exp fungi/’. The titles and abstracts were screened to identify articles that contained salient information pertaining to host defense of respiratory mycoses.DATA EXTRACTION: Information was summarized from the articles pertaining to host defense of pulmonary mycosis that had been identified by the MEDLINE search.DATA SYNTHESIS: Fungi represent a unique and highly diverse group of pathogenic organisms that have become an increasingly prevalent cause of life-threatening illness. A worldwide increase in persons with immunodeficiency has been a major contributing factor to the increase in fungal disease. As a result, clinicians are faced with an expanding array of fungal infections that pose diagnostic and therapeutic challenges. The respiratory tract is the route of acquisition for many important fungal infections; thus, understanding the host defense in the lung is an essential component of understanding host defense to fungal disease. With this understanding, fungi may be divided on the basis of the predilection of certain mycosis for specific immune defects.CONCLUSIONS: By separating fungi based on the host immune defects that predispose to disease, in conjunction with traditional divisions based on the geographic distribution of fungi, clinicians are able to focus their diagnostic efforts and to identify fungal pathogens better. In addition, an understanding of the normal host defense mechanisms that serve to control fungal infections is essential to the development of novel antifungal therapies.

scholarly journals Cellular Mechanisms of NETosis

2020 ◽  
Vol 36 (1) ◽  
pp. 191-218 ◽  
Author(s):  
Hawa Racine Thiam ◽  
Siu Ling Wong ◽  
Denisa D. Wagner ◽  
Clare M. Waterman
Keyword(s):  
Host Defense ◽  
Fungal Infections ◽  
Current Knowledge ◽  
New Drugs ◽  
Sterile Inflammation ◽  
Cellular Mechanisms ◽  
Dna Structures ◽  
Open Questions ◽  
Activated Neutrophils ◽  
Net Release

Neutrophils are critical to innate immunity, including host defense against bacterial and fungal infections. They achieve their host defense role by phagocytosing pathogens, secreting their granules full of cytotoxic enzymes, or expelling neutrophil extracellular traps (NETs) during the process of NETosis. NETs are weblike DNA structures decorated with histones and antimicrobial proteins released by activated neutrophils. Initially described as a means for neutrophils to neutralize pathogens, NET release also occurs in sterile inflammation, promotes thrombosis, and can mediate tissue damage. To effectively manipulate this double-edged sword to fight a particular disease, researchers must work toward understanding the mechanisms driving NETosis. Such understanding would allow the generation of new drugs to promote or prevent NETosis as needed. While knowledge regarding the (patho)physiological roles of NETosis is accumulating, little is known about the cellular and biophysical bases of this process. In this review, we describe and discuss our current knowledge of the molecular, cellular, and biophysical mechanisms mediating NET release as well as open questions in the field.

scholarly journals Anticandidal Activities by Lactobacillus Species: An Update on Mechanisms of Action

2021 ◽  
Vol 2 ◽  
Author(s):  
Roberto Vazquez-Munoz ◽  
Anna Dongari-Bagtzoglou
Keyword(s):  
Candida Albicans ◽  
Fungal Infection ◽  
Host Defense ◽  
Defense Mechanisms ◽  
Current Knowledge ◽  
Opportunistic Pathogen ◽  
Mechanisms Of Action ◽  
Lactobacillus Species ◽  
Antifungal Activities

Lactobacilli are among the most studied bacteria in the microbiome of the orodigestive and genitourinary tracts. As probiotics, lactobacilli may provide various benefits to the host. These benefits include regulating the composition of the resident microbiota, preventing – or even potentially reverting- a dysbiotic state. Candida albicans is an opportunistic pathogen that can influence and be influenced by other members of the mucosal microbiota and, under immune-compromising conditions, can cause disease. Lactobacillus and Candida species can colonize the same mucosal sites; however, certain Lactobacillus species display antifungal activities that can contribute to low Candida burdens and prevent fungal infection. Lactobacilli can produce metabolites with direct anticandidal function or enhance the host defense mechanisms against fungi. Most of the Lactobacillus spp. anticandidal mechanisms of action remain underexplored. This work aims to comprehensively review and provide an update on the current knowledge regarding these anticandidal mechanisms.

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