CD4 T cells producing pro-inflammatory interleukin-17 mediate high pathology in schistosomiasis

Rutitzky, Laura I.; Stadecker, Miguel J.

doi:10.1590/s0074-02762006000900052

Cited by 41 publications

(35 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data from these complementary methods provide substantial evidence that the Th17/IL-17 pathway plays a pathogenic role in H. pylori infection by promoting mucosal inflammation and contributing to bacterial colonization. A number of reports also indicate that the Th17/IL-17 pathway promotes inflammation and susceptibility in mucosal Candida albicans and Aspergillus fumigatus infections (32) and that Th17 cells are involved in the immunopathology induced by Schistosoma mansoni (33,34 this study, we found that Th1 cell responses to H. pylori were significantly reduced in IL-17 (27), recruiting inflammatory cells that infiltrate the gastric tissue and induce gastritis. In support of this, we found that IL-17 stimulated gastric epithelial cells to produce MMPs and some chemokines.…”

Section: Discussionsupporting

confidence: 59%

Helicobacter pylori-Induced Th17 Responses Modulate Th1 Cell Responses, Benefit Bacterial Growth, and Contribute to Pathology in Mice

Shi

Liu

Zhuang

et al. 2010

The Journal of Immunology

178

158

View full text Add to dashboard Cite

CD4+ T cell responses are critical for the pathogenesis of Helicobacter pylori infection. The present study evaluated the role of the Th17 subset in H. pylori infection. H. pylori infection induced significant expression of IL-17 and IFN-g in mouse gastric tissue. IL-23 and IL-12 were increased in the gastric tissue and in H. pylori-stimulated macrophages. Cell responses were examined by intracellular staining for IFN-g, IL-4, and IL-17. Mice infected with H. pylori developed a mixed Th17/Th1 response; Th17 responses preceded Th1 responses. Treatment of mice with an anti-IL-17 Ab but not a control Ab significantly reduced the H. pylori burden and inflammation in the stomach. H. pylori colonization and gastric inflammation were also lower in IL-17 2/2 mice. Furthermore, administration of recombinant adenovirus encoding mouse IL-17 increased both H. pylori load and inflammation. Further analysis showed that the Th1 cell responses to H. pylori were downregulated when IL-17 is deficient. These results together suggest that H. pylori infection induces a mixed Th17/Th1 cell response and the Th17/IL-17 pathway modulates Th1 cell responses and contributes to pathology. The Journal of Immunology, 2010, 184: 5121-5129. H elicobacter pylori is a Gram-negative, microaerophilic bacterium that resides extracellularly in the gastric mucosa and infects .50% of the population worldwide. H. pyloriinduced chronic inflammation is the cause of gastritis and peptic ulcers and a risk factor for gastric cancer (1, 2). H. pylori infection causes severe local inflammation in the gastric mucosa. CD3 + CD4 + T cells are increased in infected gastric lamina propria and play important roles in the pathogenesis of persistent H. pylori infection (3). Traditionally, CD4 + T cells are classified into two main classes: Th1 and Th2, on the basis of their cytokine secretion and immune regulatory function. Th1 cells secrete IFN-g, IL-2, and IL-12 and regulate cellular immunity, whereas Th2 cells produce IL-4, IL-5, and IL-13 and mediate humoral responses. To date, studies of immune responses to H. pylori have largely focused on Th1 and Th2 cells, and it is generally accepted that H. pylori infection results in a Th1-dominant response and that gastric inflammation largely depends on Th1 cell responses (3-6); however, IFN-g secretion alone is insufficient to induce gastritis (3). Thus, the detailed mechanism of pathogenesis is not clear. A novel subset of effector T cells, identified by secretion of IL-17, has been defined as Th17 cells. Th17 cells are distinct from Th1 and Th2 cells in their differentiation and function (7,8). TGF-b and IL-6 from activated macrophages/dendritic cells are required for Th17 cell differentiation in murine systems (9), whereas IL-12 and IFN-g promote Th1 cell development and IL-4 primes Th2 cell differentiation. The expansion and survival of Th17 cells are promoted by IL-23 (9), a heterodimeric cytokine composed of a unique p19 subunit and a p40 subunit shared with IL-12 (10). The identification of Th17 cells necessit...

show abstract

Section: Discussionsupporting

confidence: 59%

Helicobacter pylori-Induced Th17 Responses Modulate Th1 Cell Responses, Benefit Bacterial Growth, and Contribute to Pathology in Mice

Shi

Liu

Zhuang

et al. 2010

The Journal of Immunology

178

158

View full text Add to dashboard Cite

show abstract

“…However, the findings are in line with results from experimental studies on hepato-intestinal schistosomiasis. [36][37][38] To our knowledge, this study from Malawi is the first to quantify the periovular density of HIV target cells in schistosome infected cervicovaginal mucosa.…”

Section: Discussionmentioning

confidence: 97%

HIV Target Cells in Schistosoma haematobium-Infected Female Genital Mucosa

Jourdan

Holmen²,

Gundersen³

et al. 2011

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

“…We subsequently showed in the same lung migration model that IL-17A deficient animals were protected from the peak of tissue damage [46 ]. In addition, IL-17 is associated with more severe pathology in both murine and human schistosomiasis [48,49] and human onchocerchiasis [50] These data are consistent with the proposal that IL-17 pushes the type 2 response into a more pathological state [51]. The ability of IL-17 to exacerbate type 2 pathology has recently become a central focus of asthma research [reviewed in [15]].…”

Section: Il-17 and Type 2 Cytokinesmentioning

confidence: 89%

IL-17 and neutrophils: unexpected players in the type 2 immune response

Allen¹,

Sutherland²,

Rückerl³

2015

Current Opinion in Immunology

View full text Add to dashboard Cite

The study of immunity to helminth infection has been central to understanding the function of type 2 cytokines and their targets. Although type 2 cytokines are considered anti-inflammatory and promote tissue repair, they also contribute to allergy and fibrosis. Here, we utilise data from helminth infection models, to illustrate that IL-17 and neutrophils, typically associated with pro-inflammatory responses, are intimately linked with type 2 immunity. Neutrophils work with IL-4Rα-activated macrophages to control incoming larvae but this comes at a cost of enhanced tissue damage. Chitinase like proteins (CLPs) bridge these diverse outcomes, inducing both protective IL-17 and reparative Th2 responses. Dysregulation of CLPs, IL-17 and neutrophils likely contribute to disease severity and pathology associated with type 2 immunity.

show abstract

CD4 T cells producing pro-inflammatory interleukin-17 mediate high pathology in schistosomiasis

Abstract: In murine schistosomiasis mansoni, whether

Cited by 41 publications

References 39 publications

Helicobacter pylori-Induced Th17 Responses Modulate Th1 Cell Responses, Benefit Bacterial Growth, and Contribute to Pathology in Mice

Helicobacter pylori-Induced Th17 Responses Modulate Th1 Cell Responses, Benefit Bacterial Growth, and Contribute to Pathology in Mice

HIV Target Cells in Schistosoma haematobium-Infected Female Genital Mucosa

IL-17 and neutrophils: unexpected players in the type 2 immune response

Contact Info

Product

Resources

About