The Emerging Role of Mast Cells in Response to Fungal Infection

Mast cells (MCs) have been considered as the core effector cells of allergic diseases. However, there are evidence suggesting that MCs are involved in the mechanisms of fungal infection. MCs are mostly located in the border between host and environment and thus may have easy contact with the external environmental pathogens. These cells express receptors which can recognize pathogen-associated molecular patterns such as Toll-like receptors (TLR2/4) and C-type Lectins receptors (Dectin-1/2). Currently, more and more data indicate that MCs can be interacted with some fungi (Candida albicans, Aspergillus fumigatus and Sporothrix schenckii). It is demonstrated that MCs can enhance immunity through triggered degranulation, secretion of cytokines and chemokines, neutrophil recruitment, or provision of extracellular DNA traps in response to the stimulation by fungi. In contrast, the involvement of MCs in some immune responses may lead to more severe symptoms, such as intestinal barrier function loss, development of allergic bronchial pulmonary aspergillosis and increased area of inflammatory in S. schenckii infection. This suggests that MCs and their relevant signaling pathways are potential treatment regimens to prevent the clinically unwanted consequences. However, it is not yet possible to make definitive statements about the role of MCs during fungal infection and/or pathomechanisms of fungal diseases. In our article, we aim to review the function of MCs in fungal infections from molecular mechanism to signaling pathways, and illustrate the role of MCs in some common host-fungi interactions.

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Role of mast cells and probiotics in the regulation of intestinal barrier function

10.3384/diss.diva-100770 ◽

2013 ◽

Author(s):

Anders Karlsson ◽

Keyword(s):

Mast Cells ◽

Barrier Function ◽

Intestinal Barrier ◽

Intestinal Barrier Function

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Mast Cells Exert Anti-Inflammatory Effects in an IL10−/−Model of Spontaneous Colitis

Mediators of Inflammation ◽

10.1155/2018/7817360 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 8

Author(s):

E. M. Lennon ◽

L. B. Borst ◽

L. L. Edwards ◽

A. J. Moeser

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Double Knockout ◽

Significant Amelioration ◽

Anti Inflammatory ◽

Proinflammatory Role ◽

Chemical Colitis

Mast cells are well established as divergent modulators of inflammation and immunosuppression, but their role in inflammatory bowel disease (IBD) remains to be fully defined. While previous studies have demonstrated a proinflammatory role for mast cells in acute models of chemical colitis, more recent investigations have shown that mast cell deficiency can exacerbate inflammation in spontaneous colitis models, thus suggesting a potential anti-inflammatory role of mast cells in IBD. Here, we tested the hypothesis that in chronic, spontaneous colitis, mast cells are protective. We compared colitis and intestinal barrier function in IL10−/−mice to mast cell deficient/IL10−/−(double knockout (DKO): KitWsh/Wsh × IL10−/−) mice. Compared with IL10−/−mice, DKO mice exhibited more severe colitis as assessed by increased colitis scores, mucosal hypertrophy, intestinal permeability, and colonic cytokine production. PCR array analyses demonstrated enhanced expression of numerous cytokine and chemokine genes and downregulation of anti-inflammatory genes (e.g.,Tgfb2,Bmp2,Bmp4,Bmp6, andBmp7) in the colonic mucosa of DKO mice. Systemic reconstitution of DKO mice with bone marrow-derived mast cells resulted in significant amelioration of IL10−/−-mediated colitis and intestinal barrier injury. Together, the results presented here demonstrate that mast cells exert anti-inflammatory properties in an established model of chronic, spontaneous IBD. Given the previously established proinflammatory role of mast cells in acute chemical colitis models, the present findings provide new insight into the divergent roles of mast cells in modulating inflammation during different stages of colitis. Further investigation of the mechanism of the anti-inflammatory role of the mast cells may elucidate novel therapies.

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STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽

10.3390/biomedicines9020187 ◽

2021 ◽

Vol 9 (2) ◽

pp. 187

Author(s):

Lokman Pang ◽

Jennifer Huynh ◽

Mariah G. Alorro ◽

Xia Li ◽

Matthias Ernst ◽

...

Keyword(s):

Barrier Function ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Intestinal Epithelial ◽

Barrier Dysfunction ◽

Epithelial Integrity ◽

Barrier Integrity ◽

Gp130 Receptor ◽

Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

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The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway

Cells ◽

10.3390/cells9040959 ◽

2020 ◽

Vol 9 (4) ◽

pp. 959 ◽

Cited By ~ 2

Author(s):

Jefferson Antônio Leite ◽

Gabriela Pessenda ◽

Isabel C. Guerra-Gomes ◽

Alynne Karen Mendonça de Santana ◽

Camila André Pereira ◽

...

Keyword(s):

Type 1 Diabetes ◽

Gut Microbiota ◽

Bacterial Translocation ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Dna Sensor ◽

Proinflammatory Response

Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2−/−) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2−/− mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2−/− mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing β cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.

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The Role of Intestinal Barrier Function in Early Life in the Development of Colitis

Colitis ◽

10.5772/25753 ◽

2012 ◽

Cited By ~ 9

Author(s):

R.C. Anderson ◽

J.E. Dalziel ◽

P.K. Gopal ◽

S. Bassett ◽

A. Ellis ◽

...

Keyword(s):

Barrier Function ◽

Early Life ◽

Intestinal Barrier ◽

Intestinal Barrier Function

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Do Mast Cells Contribute to the Antifungal Host Defense?

Cells ◽

10.3390/cells10102510 ◽

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.

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Autopsy dissection techniques and investigations in deaths due to COVID-19 triggered fungal infections - A diagnostic review

Indian Journal of Forensic and Community Medicine ◽

10.18231/j.ijfcm.2021.043 ◽

2021 ◽

Vol 8 (4) ◽

pp. 207-213

Author(s):

Himanshi Narang ◽

Amit Patil

Keyword(s):

Fungal Infection ◽

Paranasal Sinuses ◽

Fungal Infections ◽

Invasive Disease ◽

Invasive Fungal Infections ◽

Correct Interpretation ◽

Research Papers ◽

Dissection Techniques ◽

Second Wave

The COVID-19 pandemic, which originated from Wuhan, China, has rapidly spread worldwide, including India. As India grappled with the second wave, COVID-triggered fungal infection has suddenly risen tremendously, raising a sense of panic in the country. The fungal infection in COVID-19 includes Mucormycosis and Aspergillosis, as common fungal infections primarily affecting rhino-orbital structures. Many research papers have published postmortem findings in autopsies conducted on COVID-19 decedents, thereby helping to understand this contagious disease's pathogenesis. But, with the arrival of COVID-triggered fungal infection, which is a crucial invasive disease responsible for fatality, very few research papers have commented on the postmortem findings of invasive fungal infections affecting the rhino-orbital and craniocerebral structures in COVID-19 deaths. Therefore, the role of invasive fungal infection due to COVID-19 illness must be established in the causation of deaths in COVID-19 patients. This review research deals with autopsy dissection techniques and possible postmortem findings of invasive fungal infections involving the nasal and paranasal sinuses and orbital structures in COVID-19 deaths. The findings of fungal infection affecting nasal and paranasal systems may not differ in live patients and in a deceased; however, it is essential that correct interpretation of the postmortem findings aided by pre-or post-autopsy investigations is necessary to establish the role of covid triggered fungal infection in such deaths.

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Extra-articular manifestations: inflammatory bowel disease

10.1093/med/9780198734444.003.0017 ◽

2016 ◽

Author(s):

Dirk Elewaut ◽

Heleen Cypers ◽

Matthew L. Stoll ◽

Charles O. Elson

Keyword(s):

Inflammatory Bowel Disease ◽

Intestinal Microbiota ◽

Bowel Disease ◽

Intestinal Barrier ◽

Innate Immune ◽

Intestinal Barrier Function ◽

Innate Immune Responses ◽

Susceptible Host ◽

Inflammatory Bowel

A significant overlap exists between spondyloarthritis (SpA) and inflammatory bowel disease (IBD), particularly in the IL-23/IL-17 pathway. Shared immunologic mechanisms include aberrant innate immune responses, an excess of Th1/Th17-mediated immunity, and inadequate immune regulation. Many genetic factors associated with IBD are involved in host–pathogen interactions and intestinal barrier function, and the intestinal microbiota do appear to play an important role in disease development. Hence the current hypothesis for IBD pathogenesis is that it stems from a dysregulated immune response to intestinal microbiota in a genetically susceptible host. In SpA, evidence for a role of intestinal microbiota is less abundant, but given the overlap with IBD, it is plausible that gut microbiota are important players in SpA pathogenesis as well. However, there are significant genetic differences between these two conditions, as well as differing responses to biologic therapy.

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