IL-33/ST2 Axis Plays a Protective Effect in Streptococcus pyogenes Infection through Strengthening of the Innate Immunity

Kuo, Chien-Feng; Chen, Wei‐Yu; Yu, Hai-Han; Tsai, Yu‐Hsuan; Chang, Yu Chia; Chang, Chih‐Peng; Tsao, Nina

doi:10.3390/ijms221910566

Cited by 4 publications

(3 citation statements)

References 50 publications

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“…FBXL19 has been demonstrated to target the IL-33-tumorigenicity 2 IL1RL1 axis, selectively mediating the ubiquitination and degradation of IL1RL1 to limit IL-33-induced pulmonary inflammation ( 43 ). The IL-33/IL1RL1 axis plays diverse roles in various infectious diseases, and studies have suggested that it confers a protective effect against Group A Streptococcus infection by enhancing innate immunity ( 48 ). In our study, the interaction between genotypes and the abundance of Streptococcus on the skin showed a significant association with severity of psoriasis for these 3 SNPs.…”

Section: Discussionmentioning

confidence: 99%

Significant Correlation Between Cutaneous Abundance of Streptococcus and Psoriasis Severity in Patients with FBXL19 Gene Variants

Assarsson,

Söderman,

Seifert

2024

Acta Derm Venereol

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Psoriasis results from both genetic predisposition and environmental triggers, such as Streptococcal infections. This study aimed to explore the correlation between the abundance of the Streptococcus genus on the skin and psoriasis severity in individuals carrying specific psoriasis-associated genetic variants. Studying 39 chronic plaque psoriasis patients, the elbow skin microbiome and 49 psoriasis-related single nucleotide polymorphisms (SNPs) were analysed using a MiSeq instrument for 16S rDNA sequencing, and CLC Genomic Workbench for processing and analysis. Through multivariate linear regression analysis, a positive correlation was found between Streptococcus genus abundance and psoriasis severity in patients with certain FBXL19 gene-related heterozygous SNPs (rs12924903, rs10782001, rs12445568). Conversely, a negative association was observed in patients with homozygous genotypes. Moreover, we identified an association between Streptococcus abundance and psoriasis severity in patients with genetic variants related to IL-22, ERAP1, NOS2, and ILF3. This is the first study highlighting a positive association between Streptococcus skin colonization and psoriasis severity in patients with heterozygous genotypes within the FBXL19 gene region. FXBL19 targets the IL-33/IL1RL1 axis, crucial in infectious diseases and innate immunity promotion. These novel results suggests an intricate interaction among host genetics, Streptococcus skin colonization, and psoriasis inflammation, offering potential avenues for novel treatment approaches.

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Section: Discussionmentioning

confidence: 99%

Significant Correlation Between Cutaneous Abundance of Streptococcus and Psoriasis Severity in Patients with FBXL19 Gene Variants

Assarsson,

Söderman,

Seifert

2024

Acta Derm Venereol

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“…IL-33 is a chromatin-related nuclear cytokine, which can play a variety of extracellular biological effects in full-length or truncated active forms [ 24 ]. IL-33 is believed to be involved in cytokine storms induced by a variety of pathogens, including influenza virus [ 27 ], Group A Streptococcus (GAS) [ 28 ], LCMV virus [ 25 , 29 ], COVID-19 [ 30 ], and so forth. However, the role of IL-33 in these diseases is inconsistent.…”

Section: Discussionmentioning

confidence: 99%

The Role of the IL-33/ST2 Axis in CpG-Induced Macrophage Activation Syndrome

Dong,

Gao,

et al. 2023

Journal of Immunology Research

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Background. Macrophage activation syndrome (MAS) is a fatal inflammatory condition, which is often associated with the elevation of multiple proinflammatory cytokines and multiple organ dysfunction. Previous studies have shown that ST2 contributes to T cell overactivation and plays a detrimental role in mouse models of primary hemophagocytic lymphohistiocytosis. The purpose of this study was to investigate the role of the IL-33/ST2 axis in a mouse model of MAS induced by repeated injections of cytosine–phosphate–guanine (CpG). Methods. Serum cytokines were determined using the cytometric bead array by flow cytometry. IL-33 and ST2 were detected by immunohistochemistry and real-time quantitative PCR in the liver and spleen of mice. CD3 and F4/80 in the liver were detected by immunohistochemistry. Inflammatory macrophages and effector memory T lymphocytes were detected by flow cytometry. Result. The CpG-induced MAS model was successfully induced after repeated CpG injections, presenting with hypercytokinemia and hepatosplenomegaly. The numbers of IL-33 positive cells in the liver and spleen decreased significantly, while the expression of ST2 in the liver tended to increase in the mice with MAS. IL-33 and St2 knockout mice showed similar levels of hepatosplenomegaly, peripheral blood count, and cytokine storm when compared with wild-type (WT) mice after induction of MAS. There were also no significant differences in liver pathology (including inflammatory cell infiltration of CD3 and F4/80) and levels of splenic inflammatory macrophages and effector memory T cells between the WT and knockout mice. Conclusion. These results suggested that IL-33 decreased in the liver and spleen tissues of MAS mice. Further results suggest that IL-33 and St2 knockout mice have no treatment potential in CpG-induced MAS. Thus, the IL-33/ST2 axis has little effect on the prognosis of CpG-induced MAS.

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“…In mice with Pseudomonas aeruginosa -induced keratitis, IL-33 effectively reduces inflammation by polarizing the macrophage production of anti-inflammatory mediators [ 195 ]. In addition, the IL-33/ST2 axis provides a protective effect against Streptococcus pyogenes infection by enhancing neutrophil migration and bactericidal activity [ 196 ]. In patients infected with HIV or dengue virus, the sST2 levels in sera rise [ 197 , 198 ].…”

Section: Il-33 and Immune-related Diseasesmentioning

confidence: 99%

Dual Immune Regulatory Roles of Interleukin-33 in Pathological Conditions

Guo

Bossila

et al. 2022

Cells

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Interleukin-33 (IL-33), a member of the IL-1 cytokine family and a multifunctional cytokine, plays critical roles in maintaining host homeostasis and in pathological conditions, such as allergy, infectious diseases, and cancer, by acting on multiple types of immune cells and promoting type 1 and 2 immune responses. IL-33 is rapidly released by immune and non-immune cells upon stimulation by stress, acting as an “alarmin” by binding to its receptor, suppression of tumorigenicity 2 (ST2), to trigger downstream signaling pathways and activate inflammatory and immune responses. It has been recognized that IL-33 displays dual-functioning immune regulatory effects in many diseases and has both pro- and anti-tumorigenic effects, likely depending on its primary target cells, IL-33/sST2 expression levels, cellular context, and the cytokine microenvironment. Herein, we summarize our current understanding of the biological functions of IL-33 and its roles in the pathogenesis of various conditions, including inflammatory and autoimmune diseases, infections, cancers, and cases of organ transplantation. We emphasize the nature of context-dependent dual immune regulatory functions of IL-33 in many cells and diseases and review systemic studies to understand the distinct roles of IL-33 in different cells, which is essential to the development of more effective diagnoses and therapeutic approaches for IL-33-related diseases.

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IL-33/ST2 Axis Plays a Protective Effect in Streptococcus pyogenes Infection through Strengthening of the Innate Immunity

Cited by 4 publications

References 50 publications

Significant Correlation Between Cutaneous Abundance of Streptococcus and Psoriasis Severity in Patients with FBXL19 Gene Variants

Significant Correlation Between Cutaneous Abundance of Streptococcus and Psoriasis Severity in Patients with FBXL19 Gene Variants

The Role of the IL-33/ST2 Axis in CpG-Induced Macrophage Activation Syndrome

Dual Immune Regulatory Roles of Interleukin-33 in Pathological Conditions

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