The Interactions Between Candida albicans and Mucosal Immunity

Mucosa protects the body against external pathogen invasion. However, pathogen colonies on the mucosa can invade the mucosa when the immunosurveillance is compromised, causing mucosal infection and subsequent diseases. Therefore, it is necessary to timely and effectively monitor and control pathogenic microorganisms through mucosal immunity. Candida albicans is the most prevalent fungi on the mucosa. The C. albicans colonies proliferate and increase their virulence, causing severe infectious diseases and even death, especially in immunocompromised patients. The normal host mucosal immune defense inhibits pathogenic C. albicans through stepwise processes, such as pathogen recognition, cytokine production, and immune cell phagocytosis. Herein, the current advances in the interactions between C. albicans and host mucosal immune defenses have been summarized to improve understanding on the immune mechanisms against fungal infections.

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The assimilation of different carbon sources in Candida albicans: Fitness and pathogenicity

Medical Mycology ◽

10.1093/mmy/myaa080 ◽

2020 ◽

Cited By ~ 1

Author(s):

Bronwyn Lok ◽

Mowaffaq Adam Ahmad Adam ◽

Laina Zarisa Mohd Kamal ◽

Nwakpa Anthony Chukwudi ◽

Rosline Sandai ◽

...

Keyword(s):

Candida Albicans ◽

Carbon Source ◽

Fungal Infections ◽

Carbon Sources ◽

Surface Hydrophobicity ◽

Vital Role ◽

Infection Process ◽

The Body ◽

Mycelial Form ◽

Cell Wall Biogenesis

Abstract Candida albicans is a commensal yeast commonly found on the skin and in the body. However, in immunocompromised individuals, the fungi could cause local and systemic infections. The carbon source available plays an important role in the establishment of C. albicans infections. The fungi's ability to assimilate a variety of carbon sources plays a vital role in its colonization, and by extension, its fitness and pathogenicity, as it often inhabits niches that are glucose-limited but rich in alternative carbon sources. A difference in carbon sources affect the growth and mating of C. albicans, which contributes to its pathogenicity as proliferation helps the fungi colonize its environment. The carbon source also affects its metabolism and signaling pathways, which are integral parts of the fungi's fitness and pathogenicity. As a big percentage of the carbon assimilated by C. albicans goes to cell wall biogenesis, the availability of different carbon sources will result in cell walls with variations in rigidity, adhesion, and surface hydrophobicity. In addition to the biofilm formation of the fungi, the carbon source also influences whether the fungi grow in yeast- or mycelial-form. Both forms play different roles in C. albicans’s infection process. A better understanding of the role of the carbon sources in C. albicans’s pathogenicity would contribute to more effective treatment solutions for fungal infections.

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Host Immune Defense upon Fungal Infections with Mucorales: Pathogen-Immune Cell Interactions as Drivers of Inflammatory Responses

Journal of Fungi ◽

10.3390/jof6030173 ◽

2020 ◽

Vol 6 (3) ◽

pp. 173

Author(s):

Dolly E. Montaño ◽

Kerstin Voigt

Keyword(s):

Immune Cell ◽

Inflammatory Responses ◽

Fungal Infections ◽

Immune Defense ◽

Rapid Progression ◽

Tissue Necrosis ◽

Inflammatory Processes ◽

Novel Therapeutic Strategies ◽

Potential Use ◽

Pro Inflammatory Cytokines

During the last few decades, mucormycosis has emerged as one of the most common fungal infections, following candidiasis and aspergillosis. The fungal order responsible for causing mucormycosis is the Mucorales. The main hallmarks of this infection include the invasion of blood vessels, infarction, thrombosis, and tissue necrosis, which are exhibited at the latest stages of the infection. Therefore, the diagnosis is often delayed, and the rapid progression of the infection severely endangers the life of people suffering from diabetes mellitus, hematological malignancies, or organ transplantation. Given the fact that mortality rates for mucormycosis range from 40 to 80%, early diagnosis and novel therapeutic strategies are urgently needed to battle the infection. However, compared to other fungal infections, little is known about the host immune response against Mucorales and the influence of inflammatory processes on the resolution of the infection. Hence, in this review, we summarized our current understanding of the interplay among pro-inflammatory cytokines, chemokines, and the host-immune cells in response to mucoralean fungi, as well as their potential use for immunotherapies.

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Temporal shifts in the mycobiome structure and network architecture associated with a rat (Rattus norvegicus) deep partial-thickness cutaneous burn

Medical Mycology ◽

10.1093/mmy/myz030 ◽

2019 ◽

Vol 58 (1) ◽

pp. 107-117 ◽

Cited By ~ 1

Author(s):

Fatemeh Sanjar ◽

Alan J Weaver ◽

Trent J Peacock ◽

Jesse Q Nguyen ◽

Kenneth S Brandenburg ◽

...

Keyword(s):

Network Architecture ◽

Burn Injury ◽

Fungal Infections ◽

Fungal Species ◽

Immune Defense ◽

Rat Skin ◽

Epithelial Barrier Function ◽

Pathogen Invasion ◽

Burned Skin ◽

Species Richness And Abundance

Abstract With a diverse physiological interface to colonize, mammalian skin is the first line of defense against pathogen invasion and harbors a consortium of microbes integral in maintenance of epithelial barrier function and disease prevention. While the dynamic roles of skin bacterial residents are expansively studied, contributions of fungal constituents, the mycobiome, are largely overlooked. As a result, their influence during skin injury, such as disruption of skin integrity in burn injury and impairment of host immune defense system, is not clearly delineated. Burn patients experience a high risk of developing hard-to-treat fungal infections in comparison to other hospitalized patients. To discern the changes in the mycobiome profile and network assembly during cutaneous burn-injury, a rat scald burn model was used to survey the mycobiome in healthy (n = 30) (sham-burned) and burned (n = 24) skin over an 11-day period. The healthy skin demonstrated inter-animal heterogeneity over time, while the burned skin mycobiome transitioned toward a temporally stabile community with declining inter-animal variation starting at day 3 post-burn injury. Driven primarily by a significant increase in relative abundance of Candida, fungal species richness and abundance of the burned skin decreased, especially in days 7 and 11 post-burn. The network architecture of rat skin mycobiome displayed community reorganization toward increased network fragility and decreased stability compared to the healthy rat skin fungal network. This study provides the first account of the dynamic diversity observed in the rat skin mycobiome composition, structure, and network assembly associated with postcutaneous burn injury.

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Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36

Journal of Experimental Medicine ◽

10.1084/jem.20082109 ◽

2009 ◽

Vol 206 (3) ◽

pp. 637-653 ◽

Cited By ~ 156

Author(s):

Terry K. Means ◽

Eleftherios Mylonakis ◽

Emmanouil Tampakakis ◽

Richard A. Colvin ◽

Edward Seung ◽

...

Keyword(s):

Innate Immunity ◽

Candida Albicans ◽

Caenorhabditis Elegans ◽

Antimicrobial Peptide ◽

Host Defense ◽

Fungal Pathogens ◽

Cytokine Production ◽

Scavenger Receptors ◽

Evolutionarily Conserved ◽

And Control

Receptors involved in innate immunity to fungal pathogens have not been fully elucidated. We show that the Caenorhabditis elegans receptors CED-1 and C03F11.3, and their mammalian orthologues, the scavenger receptors SCARF1 and CD36, mediate host defense against two prototypic fungal pathogens, Cryptococcus neoformans and Candida albicans. CED-1 and C03F11.1 mediated antimicrobial peptide production and were necessary for nematode survival after C. neoformans infection. SCARF1 and CD36 mediated cytokine production and were required for macrophage binding to C. neoformans, and control of the infection in mice. Binding of these pathogens to SCARF1 and CD36 was β-glucan dependent. Thus, CED-1/SCARF1 and C03F11.3/CD36 are β-glucan binding receptors and define an evolutionarily conserved pathway for the innate sensing of fungal pathogens.

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Recognition and Blocking of Innate Immunity Cells by Candida albicans Chitin

Infection and Immunity ◽

10.1128/iai.01282-10 ◽

2011 ◽

Vol 79 (5) ◽

pp. 1961-1970 ◽

Cited By ~ 111

Author(s):

Héctor M. Mora-Montes ◽

Mihai G. Netea ◽

Gerben Ferwerda ◽

Megan D. Lenardon ◽

Gordon D. Brown ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Cell Walls ◽

Mononuclear Cells ◽

Cytokine Production ◽

Immune Cell ◽

Human Peripheral Blood ◽

Immune Recognition ◽

Cell Wall Polysaccharide ◽

Content Type

ABSTRACTChitin is a skeletal cell wall polysaccharide of the inner cell wall of fungal pathogens. As yet, little about its role during fungus-host immune cell interactions is known. We show here that ultrapurified chitin fromCandida albicanscell walls did not stimulate cytokine production directly but blocked the recognition ofC. albicansby human peripheral blood mononuclear cells (PBMCs) and murine macrophages, leading to significant reductions in cytokine production. Chitin did not affect the induction of cytokines stimulated by bacterial cells or lipopolysaccharide (LPS), indicating that blocking was not due to steric masking of specific receptors. Toll-like receptor 2 (TLR2), TLR4, and Mincle (the macrophage-inducible C-type lectin) were not required for interactions with chitin. Dectin-1 was required for immune blocking but did not bind chitin directly. Cytokine stimulation was significantly reduced upon stimulation of PBMCs with heat-killed chitin-deficientC. albicanscells but not with live cells. Therefore, chitin is normally not exposed to cells of the innate immune system but is capable of influencing immune recognition by blocking dectin-1-mediated engagement with fungal cell walls.

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Mucosal Immunity andCandida albicansInfection

Clinical and Developmental Immunology ◽

10.1155/2011/346307 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 71

Author(s):

David L. Moyes ◽

Julian R. Naglik

Keyword(s):

T Cells ◽

Candida Albicans ◽

Host Defense ◽

Mucosal Immunity ◽

Immune Cell ◽

Current Knowledge ◽

Mucosal Surfaces ◽

Immune Cell Subsets ◽

Health And Disease ◽

Review Current

Interactions between mucosal surfaces and microbial microbiota are key to host defense, health, and disease. These surfaces are exposed to high numbers of microbes and must be capable of distinguishing between those that are beneficial or avirulent and those that will invade and cause disease. Our understanding of the mechanisms involved in these discriminatory processes has recently begun to expand as new studies bring to light the importance of epithelial cells and novel immune cell subsets such as Th17 T cells in these processes. Elucidating how these mechanisms function will improve our understanding of many diverse diseases and improve our ability to treat patients suffering from these conditions. In our voyage to discover these mechanisms, mucosal interactions with opportunistic commensal organisms such as the fungusCandida albicansprovide insights that are invaluable. Here, we review current knowledge of the interactions betweenC. albicansand epithelial surfaces and how this may shape our understanding of microbial-mucosal interactions.

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Innate Lymphoid Cells in Response to Intracellular Pathogens: Protection Versus Immunopathology

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.775554 ◽

2021 ◽

Vol 11 ◽

Author(s):

Anna A. Korchagina ◽

Ekaterina Koroleva ◽

Alexei V. Tumanov

Keyword(s):

Cytokine Production ◽

Immune Cell ◽

Cell Types ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Mucosal Barrier ◽

Intracellular Pathogens ◽

Pathogen Invasion ◽

And Function ◽

Mucosal Pathogens

Innate lymphoid cells (ILCs) are a heterogeneous group of cytokine-producing lymphocytes which are predominantly located at mucosal barrier surfaces, such as skin, lungs, and gastrointestinal tract. ILCs contribute to tissue homeostasis, regulate microbiota-derived signals, and protect against mucosal pathogens. ILCs are classified into five major groups by their developmental origin and distinct cytokine production. A recently emerged intriguing feature of ILCs is their ability to alter their phenotype and function in response to changing local environmental cues such as pathogen invasion. Once the pathogen crosses host barriers, ILCs quickly activate cytokine production to limit the spread of the pathogen. However, the dysregulated ILC responses can lead to tissue inflammation and damage. Furthermore, the interplay between ILCs and other immune cell types shapes the outcome of the immune response. Recent studies highlighted the important role of ILCs for host defense against intracellular pathogens. Here, we review recent advances in understanding the mechanisms controlling protective and pathogenic ILC responses to intracellular pathogens. This knowledge can help develop new ILC-targeted strategies to control infectious diseases and immunopathology.

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Binding of Candida albicans to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells

mBio ◽

10.1128/mbio.02142-16 ◽

2017 ◽

Vol 8 (2) ◽

Cited By ~ 10

Author(s):

Esther Klaile ◽

Mario M. Müller ◽

Miriam R. Schäfer ◽

Ann-Katrin Clauder ◽

Sabina Feer ◽

...

Keyword(s):

Candida Albicans ◽

Fungal Pathogen ◽

Fungal Pathogens ◽

Fungal Infections ◽

Intestinal Epithelial ◽

Behavior Understanding ◽

Mucosal Cells ◽

Human Mucosa ◽

And Control ◽

First Time

ABSTRACT Candida albicans colonizes human mucosa, including the gastrointestinal tract, as a commensal. In immunocompromised patients, C. albicans can breach the intestinal epithelial barrier and cause fatal invasive infections. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD66a), CEACAM5 (CEA), and CEACAM6 (CD66c) are immunomodulatory receptors expressed on human mucosa and are recruited by bacterial and viral pathogens. Here we show for the first time that a fungal pathogen (i.e., C. albicans) also binds directly to the extracellular domain of human CEACAM1, CEACAM3, CEACAM5, and CEACAM6. Binding was specific for human CEACAMs and mediated by the N-terminal IgV-like domain. In enterocytic C2BBe1 cells, C. albicans caused a transient tyrosine phosphorylation of CEACAM1 and induced higher expression of membrane-bound CEACAM1 and soluble CEACAM6. Lack of the CEACAM1 receptor after short hairpin RNA (shRNA) knockdown abolished CXCL8 (interleukin-8) secretion by C2BBe1 cells in response to C. albicans. In CEACAM1-competent cells, the addition of recombinant soluble CEACAM6 reduced the C. albicans-induced CXCL8 secretion. IMPORTANCE The present study demonstrates for the first time that fungal pathogens can be recognized by at least four members of the immunomodulatory CEACAM receptor family: CEACAM1, -3, -5, and -6. Three of the four receptors (i.e., CEACAM1, -5, and -6) are expressed in mucosal cells of the intestinal tract, where they are implicated in immunomodulation and control of tissue homeostasis. Importantly, the interaction of the major fungal pathogen in humans Candida albicans with CEACAM1 and CEACAM6 resulted in an altered epithelial immune response. With respect to the broad impact of CEACAM receptors on various aspects of the innate and the adaptive immune responses, in particular epithelial, neutrophil, and T cell behavior, understanding the role of CEACAMs in the host response to fungal pathogens might help to improve management of superficial and systemic fungal infections. The present study demonstrates for the first time that fungal pathogens can be recognized by at least four members of the immunomodulatory CEACAM receptor family: CEACAM1, -3, -5, and -6. Three of the four receptors (i.e., CEACAM1, -5, and -6) are expressed in mucosal cells of the intestinal tract, where they are implicated in immunomodulation and control of tissue homeostasis. Importantly, the interaction of the major fungal pathogen in humans Candida albicans with CEACAM1 and CEACAM6 resulted in an altered epithelial immune response. With respect to the broad impact of CEACAM receptors on various aspects of the innate and the adaptive immune responses, in particular epithelial, neutrophil, and T cell behavior, understanding the role of CEACAMs in the host response to fungal pathogens might help to improve management of superficial and systemic fungal infections.

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Clinical application of presepsin as diagnostic biomarker of infection: overview and updates

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0643 ◽

2019 ◽

Vol 58 (1) ◽

pp. 11-17 ◽

Cited By ~ 4

Author(s):

Emanuela Galliera ◽

Luca Massaccesi ◽

Elena de Vecchi ◽

Giuseppe Banfi ◽

Massimiliano M. Corsi Romanelli

Keyword(s):

Intensive Care ◽

Bacterial Infection ◽

Pulmonary Infection ◽

Immune Cell ◽

Fungal Infections ◽

Neonatal Infection ◽

Diagnostic Biomarker ◽

Infective Disease ◽

Immune Cell Response ◽

And Control

Abstract The appropriate identification of bacterial infection is the basis for effective treatment and control of infective disease. Among this context, an emerging biomarker of infection is presepsin (PSP), recently described as early marker of different infections. PSP secretion has been shown to be associated with monocyte phagocytosis and plasmatic levels of PSP increase in response to bacterial infection and decrease after antibiotic treatment, therefore it can be considered a marker of activation of immune cell response towards an invading pathogen. Different methods have been developed to measure PSP and this review will briefly describe the different clinical fields of application of PSP, ranging from intensive care to neonatal infection, to orthopedic and pulmonary infection as well as fungal infections and cardiovascular infections.

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Dectin-1 Is Not Required for Controlling Candida albicans Colonization of the Gastrointestinal Tract

Infection and Immunity ◽

10.1128/iai.00559-12 ◽

2012 ◽

Vol 80 (12) ◽

pp. 4216-4222 ◽

Cited By ~ 35

Author(s):

Simon Vautier ◽

Rebecca A. Drummond ◽

Pierre Redelinghuys ◽

Graeme I. Murray ◽

Donna M. MacCallum ◽

...

Keyword(s):

Candida Albicans ◽

Gastrointestinal Tract ◽

Cytokine Production ◽

Fungal Infections ◽

Systemic Infection ◽

Oral Infection ◽

Content Type ◽

Gastrointestinal Colonization ◽

Systemic Infections ◽

Recognition Receptor

ABSTRACTCandida albicansis normally found as a commensal microbe, commonly colonizing the gastrointestinal tract in humans. However, this fungus can also cause mucosal and systemic infections once immune function is compromised. Dectin-1 is an innate pattern recognition receptor essential for the control of fungal infections in both mice and humans; however, its role in the control ofC. albicanscolonization of the gastrointestinal tract has not been defined. Here, we demonstrate that in mice dectin-1 is essential for the control of gastrointestinal invasion during systemic infection, with dectin-1 deficiency associating with impaired fungal clearance and dysregulated cytokine production. Surprisingly, however, following oral infection, dectin-1 was not required for the control of mucosal colonization of the gastrointestinal tract, in terms of either fungal burdens or cytokine response. Thus, in mice, dectin-1 is essential for controlling systemic infection withC. albicansbut appears to be redundant for the control of gastrointestinal colonization.

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