<i>Aspergillus</i><i>fumigatus</i>Recognition by Dendritic Cells Negatively Regulates Allergic Lung Inflammation through a TLR2/MyD88 Pathway

Percier, Pauline; Prins, Sofie De; Tima, Giresse; Beyaert, Rudi; Grooten, Johan; Romano, Márta; Denis, Olivier

doi:10.1165/rcmb.2020-0083oc

Cited by 11 publications

(5 citation statements)

References 48 publications

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“…The results showed that PAMPs recognized by TLR2 upregulated IL-10 and decreased the recruitment of pulmonary eosinophils, thus downregulating Th2 response. 370 , 371 In allergic asthma, TLR9–IL-2 affects the Th2 response by regulating the expression of IL-17A, so small molecule inhibitors targeting TLR9 may become a new treatment strategy. 372 …”

Section: Prr-related Diseasesmentioning

confidence: 99%

Pattern recognition receptors in health and diseases

2021

Sig Transduct Target Ther

731

515

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Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into the following five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are basically composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. In recent years, the increased researches on the recognition and binding of PRRs and their ligands have greatly promoted the understanding of different PRRs signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes in detail the history, the structural characteristics, ligand recognition mechanism, the signaling pathway, the related disease, new drugs in clinical trials and clinical therapy of different types of PRRs, and discusses the significance of the research on pattern recognition mechanism for the treatment of PRR-related diseases.

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Section: Prr-related Diseasesmentioning

confidence: 99%

Pattern recognition receptors in health and diseases

2021

Sig Transduct Target Ther

731

515

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“…Many of identified asthma susceptibility genes, including IRAK-M, are expressed by airway epithelial cells, and dysregulated airway epithelial function is thought to be critical for controlling disease induction [ 6 , 15 ]. Upon stimulation with aeroallergens, airway epithelial cells, via TLRs (including TLR 2 and 4), release the early epithelial-derived cytokine and chemokines leading to the activation of innate immunity that mediate the type 2 inflammatory responses in the airways [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

IRAK-M has effects in regulation of lung epithelial inflammation

Zheng

Liu

et al. 2023

Respir Res

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Background Epithelial barrier is important for asthma development by shaping immune responses. Airway expressing-IL-1 receptor-associated kinase (IRAK)-M of Toll-like receptor pathway was involved in immunoregulation of airway inflammation through influencing activities of macrophages and dendritic cells or T cell differentiation. Whether IRAK-M has effect on cellular immunity in airway epithelial cells upon stimulation remains unclear. Methods We modeled cellular inflammation induced by IL-1β, TNF-α, IL-33, and house dust mite (HDM) in BEAS-2B and A549 cells. Cytokine production and pathway activation were used to reflect the effects of IRAK-M siRNA knockdown on epithelial immunity. Genotyping an asthma-susceptible IRAK-M SNP rs1624395 and measurement of serum CXCL10 levels were performed in asthma patients. Results IRAK-M expression was significantly induced in BEAS-2B and A549 cells after inflammatory stimulation. IRAK-M knockdown increased the lung epithelial production of cytokines and chemokines, including IL-6, IL-8, CXCL10, and CXCL11, at both mRNA and protein levels. Upon stimulation, IRAK-M silencing led to overactivation of JNK and p38 MAPK in lung epithelial cells. While antagonizing JNK or p38 MAPK inhibited increased secretion of CXCL10 in IRAK-M silenced-lung epithelium. Asthma patients carrying G/G genotypes had significantly higher levels of serum CXCL10 than those carrying homozygote A/A. Conclusion Our findings suggested that IRAK-M has effect on lung epithelial inflammation with an influence on epithelial secretion of CXCL10 partly mediated through JNK and p38 MAPK pathways. IRAK-M modulation might indicate a new insight into asthma pathogenesis from disease origin.

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“…The studies concerning the signaling pathway of immune response of MCs in A. fumigatus infection are scarce. In dendritic cells, TLR2/MyD88 signaling pathway has been proved to regulate immune response to A. fumigatus conidia, which results in a development of Th2 response ( 51 ).…”

Section: Mcs and Fungimentioning

confidence: 99%

The Emerging Role of Mast Cells in Response to Fungal Infection

Song

Liu

et al. 2021

Front. Immunol.

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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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AspergillusfumigatusRecognition by Dendritic Cells Negatively Regulates Allergic Lung Inflammation through a TLR2/MyD88 Pathway

Cited by 11 publications

References 48 publications

Pattern recognition receptors in health and diseases

Pattern recognition receptors in health and diseases

IRAK-M has effects in regulation of lung epithelial inflammation

The Emerging Role of Mast Cells in Response to Fungal Infection

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