An SNP selection strategy identified IL-22 associating with susceptibility to tuberculosis in Chinese

Zhang, Guoliang; Chen, Xinchun; Long, Chan; Zhang, Mingxia; Zhu, Bo; Wang, Lantian; Zhu, Xiu-Yun; Zhang, Jieyun; Zhou, Boping; Wang, Junwen

doi:10.1038/srep00020

Cited by 44 publications

(55 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with our results, it was previously demonstrated that the IL-22 response also dominated over the IL-17 response in patients with pulmonary tuberculosis (46). Moreover, IL-22 was shown to be important in the defense against multiple pulmonary pathogens including Mycobacterium tuberculosis (14,46,47), Klebsiella pneumoniae (48), and influenza A virus (16). Because the host defense against these pulmonary pathogens seems to strongly rely on IL-22, we hypothesize that IL-22 might play a pivotal role in the human anti-Aspergillus pulmonary host defense.…”

Section: Discussionsupporting

confidence: 80%

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

Section: Discussionsupporting

confidence: 80%

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

show abstract

“…This will provide answers pertaining to this subset and transcriptional signatures in patients from an endemic area or with different disease states. Our transcriptional analysis revealed that CCR6 + CXCR3 + CCR4 − cells preferentially express CCR2 and IL12 receptor and upon activation produce large amounts of CCL4 and IL-22, all of which have been implicated in higher susceptibility to TB infection (22, 23, 30, 31). Understanding the characteristics of CCR6 + CXCR3 + CCR4 − cells that provide them with the ability to contain TB infection should in turn provide better correlates of efficacy for TB vaccine development, which are currently lacking, and might also suggest specific pathways that can be exploited for development of antimycobacterial drugs.…”

Section: Discussionmentioning

confidence: 92%

“…CSF-1 has also been shown to play a role in the adaptive immune response against TB (29). Interestingly, mutations in the CCL4 (30) and IL22 (31) loci have been associated with increased susceptibility to TB. Overall, these data reinforce that CCR6 + CXCR3 + CCR4 − cells are capable of producing a broad spectrum of cytokines that contribute to their ability to contain LTBI.…”

Section: Resultsmentioning

confidence: 99%

Transcriptional Profile of Tuberculosis Antigen–Specific T Cells Reveals Novel Multifunctional Features

Arlehamn

Seumois

Герасимова

et al. 2014

The Journal of Immunology

113

View full text Add to dashboard Cite

In latent tuberculosis infection (LTBI) spread of the bacteria is contained by a persistent immune response, which includes CD4+ T cells as important contributors. Here we show that TB-specific CD4+ T cells have a characteristic chemokine expression signature (CCR6+CXCR3+CCR4−), and that the overall number of these cells is significantly increased in LTBI donors compared to healthy subjects. We have comprehensively characterized the transcriptional signature of CCR6+CXCR3+CCR4− cells and find significant differences to conventional Th1, Th17 and Th2 cells, but no major changes between healthy and LTBI donors. CCR6+CXCR3+CCR4− cells display linage-specific signatures of both Th1 and Th17 cells, but also have a unique gene expression program including genes associated with susceptibility to TB, enhanced T cell activation, enhanced cell survival, and induction of a cytotoxic program akin to CTL cells. Overall, the gene expression signature of CCR6+CXCR3+CCR4− cells reveals characteristics important for controlling latent TB infections.

show abstract

“…Isolated DNA was stored at −80°C before usage. SNPs were selected according to methods described previously [16], with focusing on their potential regulatory roles, such as transcription binding sites in the promoter region, microRNA target sites in the 3′ untranslated region (UTR), protein phosphorylation sites in the extrons and other putative regulation sites.…”

Section: Methodsmentioning

confidence: 99%

Genetic variants in IL1A and IL1B contribute to the susceptibility to 2009 pandemic H1N1 influenza A virus

Liu

Zhang

et al. 2013

BMC Immunol

Self Cite

View full text Add to dashboard Cite

BackgroundHost genetic variations may contribute to disease susceptibility of influenza. IL-1A and IL-1B are important inflammatory cytokines that mediate the inflammation and initiate the immune response against virus infection. In this study, we investigated the relationship between single-nucleotide polymorphisms (SNPs) of Interleukin-1A (IL-1A) and Interleukin-1B (IL-1B) and the susceptibility to 2009 pandemic A/H1N1 influenza (A(H1N1)pdm09). 167 patients whom were confirmed with A(H1N1)pdm09 and 192 healthy controls were included in this study. Four SNPs (rs1304037, rs16347, rs17561, rs2071373) in IL1A gene and three SNPs (rs1143623, rs3917345, rs1143627) in IL1B gene were genotyped by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform, and the associations of the genetic variants of IL-1 with susceptibility to A(H1N1)pdm09 were then assessed.ResultsThe polymorphisms of rs17561 in IL1A gene and rs1143627 in IL1B gene were found to be associated with susceptibility to A(H1N1)pdm09 with P values of 0.003 (OR 2.08, 95% CI 1.27-3.41) and 0.002 (OR 1.62 , 95% CI 1.20-2.18), respectively. However, no significant difference in allelic frequency was observed for other SNPs between cases and controls.ConclusionsThis study provides a new insight into pathogenesis of A(H1N1)pdm09, suggesting that genetic variants of IL-1A and IL-1B may exert a substantial impact on the susceptibility of A(H1N1)pdm09 virus infection.

show abstract

An SNP selection strategy identified IL-22 associating with susceptibility to tuberculosis in Chinese

Cited by 44 publications

References 35 publications

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

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

Transcriptional Profile of Tuberculosis Antigen–Specific T Cells Reveals Novel Multifunctional Features

Genetic variants in IL1A and IL1B contribute to the susceptibility to 2009 pandemic H1N1 influenza A virus

Contact Info

Product

Resources

About