IL‐22 and TNF‐α represent a key cytokine combination for epidermal integrity during infection with <i>Candida albicans</i>

Eyerich, Stefanie; Wagener, Jeanette; Wenzel, Vera; Scarponi, Claudia; Pennino, Davide; Albanesi, Cristina; Schaller, Martin; Behrendt, Heidrun; Ring, Johannes; Schmidt‐Weber, Carsten B.; Cavani, Andrea; Mempel, Martin; Traidl‐Hoffmann, Claudia; Eyerich, Kilian

doi:10.1002/eji.201041197

Cited by 125 publications

(114 citation statements)

References 35 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…Both cytokines are produced by Th22 cells and can synergistically induce an effective innate immune response of epithelial cells during C. albicans infection, conferring protection in humans (Eyerich et al, 2011). Our results indicate that there are potential microbial factors that correlate with the production of both cytokines.…”

Section: Functional Associations With Fungal-induced Cytokine Responsesmentioning

confidence: 66%

Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity

Schirmer¹,

Smeekens²,

Vlamakis³

et al. 2016

Cell

231

196

View full text Add to dashboard Cite

SummaryGut microbial dysbioses are linked to aberrant immune responses, which are often accompanied by abnormal production of inflammatory cytokines. As part of the Human Functional Genomics * Correspondence: xavier@molbio.mgh.harvard.edu (R.J.X.), mihai.netea@radboudumc.nl (M.G.N.). Lead ContactPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Author ContributionsMS performed the metagenomics data analyses and correlation analyses. SPS, MJ, MO, AK, and MJB performed the immunological assays and processed and analyzed the data. MS, HV, EAF, CH, MGN, and RJX interpreted the results. MS, EAF, and CH led the computational methods and research development. SPS, MJ, and MO collected clinical samples. SPS, TJ, and LJ performed functional validation experiments. MS, SPS, HV, CH, MGN, and RJX assembled and wrote the paper. MS, HV, MGN, and RJX served as project leaders. JF, AZ, LABJ, CW, MGN, and RJX designed the cohort study. CH, CW, MGN, and RJX served as principal investigators. Table S1. Related to Figure 3. Correlation coefficients for all significant species associations Table S2. Related to Figure 3. FDR values for all significant species associations Table S3. Related to Figure 3. Correlation coefficients for all significant genus associations Table S4. Related to Figure 3. FDR values for all significant genus associations Table S5. Related to Figure 4. Correlation coefficients for all significant pathway associations Table S6. Related to Figure 4. FDR values for all significant pathway associations Table S7. Related to Figure 4. Correlation coefficients for all significant GO category associations Table S8. Related to Figure 4. FDR values for all significant GO category associations HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptProject (HFGP), we investigate how differences in composition and function of gut microbial communities may contribute to inter-individual variation in cytokine responses to microbial stimulations in healthy humans. We observe microbiome-cytokine interaction patterns that are stimulus-specific, cytokine-specific, and cytokine-and stimulus-specific. Validation of two predicted host-microbial interactions reveal that TNFα and IFNγ production are associated with specific microbial metabolic pathways: palmitoleic acid metabolism and tryptophan degradation to tryptophol. Besides providing a resource of predicted microbially-derived mediators that influence immune phenotypes in response to common microorganisms, these data can help to define principles for understanding disease susceptibility. The three HFGP stud...

show abstract

Section: Functional Associations With Fungal-induced Cytokine Responsesmentioning

confidence: 66%

Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity

Schirmer¹,

Smeekens²,

Vlamakis³

et al. 2016

Cell

231

196

View full text Add to dashboard Cite

show abstract

“…2A). To determine whether the IL-22 + cells in our experiments match the phenotype of previously described Th22 cells, we assessed whether these cells coexpressed TNF-a, a characteristic of Th22 cells (15,19,27). Indeed, most IL-22 + cells coexpressed TNF-a (Fig.…”

Section: Il-22 Is Not Restricted To a Specific Th Cell Subsetmentioning

confidence: 76%

Aspergillus fumigatus–Induced IL-22 Is Not Restricted to a Specific Th Cell Subset and Is Dependent on Complement Receptor 3

Gresnigt

Becker

Smeekens

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Th cell responses induced by Aspergillus fumigatus have been extensively investigated in mouse models. However, the requirements for differentiation and the characteristics of A. fumigatus–induced human Th cell subsets remain poorly defined. We demonstrate that A. fumigatus induces Th1 and Th17 subsets in human PBMCs. Moreover, we show that the cytokine IL-22 is not restricted to a specific Th subset, in contrast to IL-17A. The pattern recognition and cytokine pathways that skew these Aspergillus-induced Th cell responses are TLR4- and IL-1–, IL-23–, and TNF-α–dependent. These pathways are of specific importance for production of the cytokines IL-17A and IL-22. Additionally, our data reveal that the dectin-1/Syk pathway is redundant and that TLR2 has an inhibitory effect on Aspergillus-induced IL-17A and IL-22 production. Notably, blocking complement receptor (CR)3 significantly reduced Aspergillus-induced Th1 and Th17 responses, and this was independent on the activation of the complement system. CR3 is a known receptor for β-1,3-glucan; however, blocking CR3 had significant effects on Th cell responses induced by heat-killed Aspergillus conidia, which have minimal β-glucan expression on their cell surface. Collectively, these data characterize the human Th cell subsets induced by Aspergillus, demonstrate that the capability to produce IL-22 is not restricted to a specific T cell subset, and provide evidence that CR3 might play a significant role in the adaptive host defense against Aspergillus, although the ligand and its action remain to be elucidated.

show abstract

“…73 In primary human keratinocytes, IL-22 plus TNF-a effectively inhibit the growth of C. albicans and maintain the survival of epithelia. 85 In addition, human vaginal epithelial cells could express S100 calcium-binding proteins to recruit polymorphonuclear neutrophils (PMNs) to the C. albicans-infected vagina. 86 Recently it was shown that S100A8 alarmin is sufficient, but not necessary, to induce PMN migration during experimental vaginal candidiasis.…”

Section: Prrs Of Epithelial Cellsmentioning

confidence: 99%