scholarly journals Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis

2009 ◽  
Vol 206 (2) ◽  
pp. 299-311 ◽  
Author(s):  
Heather R. Conti ◽  
Fang Shen ◽  
Namrata Nayyar ◽  
Eileen Stocum ◽  
Jianing N. Sun ◽  
...  
Keyword(s):  
Host Defense ◽  
Th17 Cells ◽  
Oral Candidiasis ◽  
Gene Profiling ◽  
Anatomical Location ◽  
T Helper 1 ◽  
Signature Genes ◽  
Mucosal Candidiasis ◽  
Disseminated Disease

The commensal fungus Candida albicans causes oropharyngeal candidiasis (OPC; thrush) in settings of immunodeficiency. Although disseminated, vaginal, and oral candidiasis are all caused by C. albicans species, host defense against C. albicans varies by anatomical location. T helper 1 (Th1) cells have long been implicated in defense against candidiasis, whereas the role of Th17 cells remains controversial. IL-17 mediates inflammatory pathology in a gastric model of mucosal candidiasis, but is host protective in disseminated disease. Here, we directly compared Th1 and Th17 function in a model of OPC. Th17-deficient (IL-23p19−/−) and IL-17R–deficient (IL-17RA−/−) mice experienced severe OPC, whereas Th1-deficient (IL-12p35−/−) mice showed low fungal burdens and no overt disease. Neutrophil recruitment was impaired in IL-23p19−/− and IL-17RA−/−, but not IL-12−/−, mice, and TCR-αβ cells were more important than TCR-γδ cells. Surprisingly, mice deficient in the Th17 cytokine IL-22 were only mildly susceptible to OPC, indicating that IL-17 rather than IL-22 is vital in defense against oral candidiasis. Gene profiling of oral mucosal tissue showed strong induction of Th17 signature genes, including CXC chemokines and β defensin-3. Saliva from Th17-deficient, but not Th1-deficient, mice exhibited reduced candidacidal activity. Thus, the Th17 lineage, acting largely through IL-17, confers the dominant response to oral candidiasis through neutrophils and antimicrobial factors.

scholarly journals IL-17A and Th17 Cells in Lung Inflammation: An Update on the Role of Th17 Cell Differentiation and IL-17R Signaling in Host Defense against Infection

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Hsing-Chuan Tsai ◽  
Sharlene Velichko ◽  
Li-Yin Hung ◽  
Reen Wu
Keyword(s):  
Cell Differentiation ◽  
Host Defense ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Critical Role ◽  
Klebsiella Pneumonia ◽  
Antimicrobial Proteins ◽  
Cytokines And Chemokines ◽  
Th17 Cell Differentiation

The significance of Th17 cells and interleukin- (IL-)17A signaling in host defense and disease development has been demonstrated in various infection and autoimmune models. Numerous studies have indicated that Th17 cells and its signature cytokine IL-17A are critical to the airway’s immune response against various bacteria and fungal infection. Cytokines such as IL-23, which are involved in Th17 differentiation, play a critical role in controllingKlebsiella pneumonia(K. pneumonia) infection. IL-17A acts on nonimmune cells in infected tissues to strengthen innate immunity by inducing the expression of antimicrobial proteins, cytokines, and chemokines. Mice deficient in IL-17 receptor (IL-17R) expression are susceptible to infection by various pathogens. In this review, we summarize the recent advances in unraveling the mechanism behind Th17 cell differentiation, IL-17A/IL-17R signaling, and also the importance of IL-17A in pulmonary infection.

IL-17A, IL-22, and IL-23 as Markers of Psoriasis Activity

2015 ◽  
Vol 19 (6) ◽  
pp. 555-560 ◽  
Author(s):  
Christina Fotiadou ◽  
Elizabeth Lazaridou ◽  
Eleni Sotiriou ◽  
Spiridon Gerou ◽  
Athanasios Kyrgidis ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Tumor Necrosis ◽  
Serum Levels ◽  
Sensitivity Analyses ◽  
T Helper ◽  
T Helper 1 ◽  
Factor Α ◽  
Necrosis Factor ◽  
Active Disease

Introduction: T-helper 1 (Th1), Th17 cells, and their related cytokines are implicated in psoriasis pathogenesis although the contribution of each group of cytokines in psoriasis activity has not been fully clarified. Objectives: To investigate whether Th17-related cytokines are associated with psoriasis activity. Methods: The serum levels of interleukin (IL)-1β, 6, 8, 17Α, 22, 23, and tumor necrosis factor-α (TNFα) were measured with flow cytometry in 35 patients with plaque psoriasis (21 with stable and 14 with active disease) and in 20 healthy controls. Results: Interleukin-6, 8, 17A, 22, 23, and TNFα were significantly elevated in psoriasis patients compared with controls. In the sensitivity analyses, patients with active disease showed significantly increased levels of IL-17A, IL-23, and IL-22 as compared to the group of patients with stable psoriasis. Conclusions: Our study highlights a possible crucial role of IL-17A, IL-22, and IL-23 in the activity of psoriasis and the early stages of the disease.

scholarly journals Interleukin-17-Induced Protein Lipocalin 2 Is Dispensable for Immunity to Oral Candidiasis

2013 ◽  
Vol 82 (3) ◽  
pp. 1030-1035 ◽  
Author(s):  
Maria Carolina Ferreira ◽  
Natasha Whibley ◽  
Anna J. Mamo ◽  
Ulrich Siebenlist ◽  
Yvonne R. Chan ◽  
...  
Keyword(s):  
Host Defense ◽  
Iron Acquisition ◽  
Oral Candidiasis ◽  
Oral Infection ◽  
Interleukin 17 ◽  
Chronic Mucocutaneous Candidiasis ◽  
Lipocalin 2 ◽  
Content Type ◽  
Neutrophil Gelatinase Associated Lipocalin

ABSTRACTOropharyngeal candidiasis (OPC; thrush) is an opportunistic fungal infection caused by the commensal microbeCandida albicans. Immunity to OPC is strongly dependent on CD4+T cells, particularly those of the Th17 subset. Interleukin-17 (IL-17) deficiency in mice or humans leads to chronic mucocutaneous candidiasis, but the specific downstream mechanisms of IL-17-mediated host defense remain unclear. Lipocalin 2 (Lcn2; 24p3; neutrophil gelatinase-associated lipocalin [NGAL]) is an antimicrobial host defense factor produced in response to inflammatory cytokines, particularly IL-17. Lcn2 plays a key role in preventing iron acquisition by bacteria that use catecholate-type siderophores, and lipocalin 2−/−mice are highly susceptible to infection byEscherichia coliandKlebsiella pneumoniae. The role of Lcn2 in mediating immunity to fungi is poorly defined. Accordingly, in this study, we evaluated the role of Lcn2 in immunity to oral infection withC. albicans. Lcn2 is strongly upregulated following oral infection withC. albicans, and its expression is almost entirely abrogated in mice with defective IL-17 signaling (IL-17RA−/−or Act1−/−mice). However, Lcn2−/−mice were completely resistant to OPC, comparably to wild-type (WT) mice. Moreover, Lcn2 deficiency mediated protection from OPC induced by steroid immunosuppression. Therefore, despite its potent regulation duringC. albicansinfection, Lcn2 is not required for immunity to mucosal candidiasis.

scholarly journals Role of Dectin-2 for Host Defense against Systemic Infection with Candida glabrata

2013 ◽  
Vol 82 (3) ◽  
pp. 1064-1073 ◽  
Author(s):  
Daniela C. Ifrim ◽  
Judith M. Bain ◽  
Delyth M. Reid ◽  
Marije Oosting ◽  
Ineke Verschueren ◽  
...  
Keyword(s):  
Host Defense ◽  
Candida Glabrata ◽  
Defense Mechanisms ◽  
Systemic Infection ◽  
Immune Recognition ◽  
T Helper 1 ◽  
Content Type ◽  
Susceptibility To Infection ◽  
Lower Production

ABSTRACTAlthoughCandida glabratais an important pathogenicCandidaspecies, relatively little is known about its innate immune recognition. Here, we explore the potential role of Dectin-2 for host defense againstC. glabrata. Dectin-2-deficient (Dectin-2−/−) mice were found to be more susceptible toC. glabratainfections, showing a defective fungal clearance in kidneys but not in the liver. The increased susceptibility to infection was accompanied by lower production of T helper 1 (Th1) and Th17-derived cytokines by splenocytes of Dectin-2−/−mice, while macrophage-derived cytokines were less affected. These defects were associated with a moderate yet significant decrease in phagocytosis of the fungus by the Dectin-2−/−macrophages and neutrophils. Neutrophils of Dectin-2−/−mice also displayed lower production of reactive oxygen species (ROS) upon challenge with opsonizedC. glabrataorC. albicans. This study suggests that Dectin-2 is important in host defense againstC. glabrataand provides new insights into the host defense mechanisms against this important fungal pathogen.

Role of the macrophage-inducible C-type lectin Mincle in the lung host defense against mycobacterial infections in mice

Pneumologie ◽  
2011 ◽  
Vol 65 (12) ◽  
Author(s):  
F Behler ◽  
K Steinwede ◽  
R Maus ◽  
J Bohling ◽  
UA Maus
Keyword(s):  
Host Defense ◽  
Mycobacterial Infections

scholarly journals Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells

2020 ◽  
Vol 117 (48) ◽  
pp. 30639-30648
Author(s):  
Dan Hu ◽  
Emily C. Tjon ◽  
Karin M. Andersson ◽  
Gabriela M. Molica ◽  
Minh C. Pham ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Transcription Factor ◽  
Proinflammatory Cytokines ◽  
Th17 Cells ◽  
Gene Set Enrichment Analysis ◽  
Aberrant Expression ◽  
Signature Genes ◽  
The Impact

IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA−CD4+T (CCR6+T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targetingUSF2in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.

scholarly journals Adipose Tissue Immunomodulation and Treg/Th17 Imbalance in the Impaired Glucose Metabolism of Children with Obesity

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 554
Author(s):  
Stefania Croce ◽  
Maria Antonietta Avanzini ◽  
Corrado Regalbuto ◽  
Erika Cordaro ◽  
Federica Vinci ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Th17 Cells ◽  
Metabolic Disorders ◽  
Potential Role ◽  
Immune Monitoring ◽  
Metabolic Dysfunction ◽  
Impaired Glucose Metabolism ◽  
T Cell Infiltration

In the last few decades, obesity has increased dramatically in pediatric patients. Obesity is a chronic disease correlated with systemic inflammation, characterized by the presence of CD4 and CD8 T cell infiltration and modified immune response, which contributes to the development of obesity related diseases and metabolic disorders, including impaired glucose metabolism. In particular, Treg and Th17 cells are dynamically balanced under healthy conditions, but imbalance occurs in inflammatory and pathological states, such as obesity. Some studies demonstrated that peripheral Treg and Th17 cells exhibit increased imbalance with worsening of glucose metabolic dysfunction, already in children with obesity. In this review, we considered the role of adipose tissue immunomodulation and the potential role played by Treg/T17 imbalance on the impaired glucose metabolism in pediatric obesity. In the patient care, immune monitoring could play an important role to define preventive strategies of pediatric metabolic disease treatments.

scholarly journals Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

2020 ◽  
Vol 7 ◽  
Author(s):  
Mark Nomden ◽  
Leonie Beljaars ◽  
Henkjan J. Verkade ◽  
Jan B. F. Hulscher ◽  
Peter Olinga
Keyword(s):  
Immune Response ◽  
Liver Fibrosis ◽  
Pulmonary Fibrosis ◽  
Matrix Metalloproteinase ◽  
Biliary Atresia ◽  
Adaptive Immune Response ◽  
Cell Contact ◽  
T Helper 1 ◽  
Matrix Metalloproteinase 7

Biliary atresia (BA) is a rare cholangiopathy of infancy in which the bile ducts obliterate, leading to profound cholestasis and liver fibrosis. BA is hypothesized to be caused by a viral insult that leads to over-activation of the immune system. Patients with BA are surgically treated with a Kasai portoenterostomy (KPE), which aims to restore bile flow from the liver to the intestines. After KPE, progressive liver fibrosis is often observed in BA patients, even despite surgical success and clearance of their jaundice. The innate immune response is involved during the initial damage to the cholangiocytes and further differentiation of the adaptive immune response into a T-helper 1 cell (Th1) response. Multiple studies have shown that there is continuing elevation of involved cytokines that can lead to the progressive liver fibrosis. However, the mechanism by which the progressive injury occurs is not fully elucidated. Recently, matrix metalloproteinase-7 (MMP-7) has been investigated to be used as a biomarker to diagnose BA. MMPs are involved in extracellular matrix (ECM) turnover, but also have non-ECM related functions. The role of MMP-7 and other MMPs in liver fibrosis is just starting to be elucidated. Multiple studies have shown that serum MMP-7 measurements are able to accurately diagnose BA in a cohort of cholestatic patients while hepatic MMP-7 expression correlated with BA-related liver fibrosis. While the mechanism by which MMP-7 can be involved in the pathophysiology of BA is unclear, MMP-7 has been investigated in other fibrotic pathologies such as renal and idiopathic pulmonary fibrosis. MMP-7 is involved in Wnt/β-catenin signaling, reducing cell-to-cell contact by shedding of E-cadherin, amplifying inflammation and fibrosis via osteopontin (OPN) and TNF-α while it also appears to play a role in induction of angiogenesis This review aims to describe the current understandings of the pathophysiology of BA. Subsequently, we describe how MMP-7 is involved in other pathologies, such as renal and pulmonary fibrosis. Then, we propose how MMP-7 can potentially be involved in BA. By doing this, we aim to describe the putative role of MMP-7 as a prognostic biomarker in BA and to provide possible new therapeutic and research targets that can be investigated in the future.

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