scholarly journals Role of chemokine ligand 2 in the protective response to early murine pulmonary tuberculosis

Immunology ◽  
2003 ◽  
Vol 109 (4) ◽  
pp. 547-551 ◽  
Author(s):  
Andre Kipnis ◽  
Randall J. Basaraba ◽  
Ian M. Orme ◽  
Andrea M. Cooper
2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Sanjay K. Biswas ◽  
Mayank Mittal ◽  
Ekata Sinha ◽  
Vandana Singh ◽  
Nidhi Arela ◽  
...  

The C-C motif chemokine ligand-2 (CCL2) was evidenced to be associated with tuberculosis susceptibility in some ethnic groups. In the present study, effort was made to find out the association of CCL2-2518 A>G and -362 G>C variants with susceptibility to TB in a population from North India. The genotyping was carried out in 373 participants with pulmonary TB (PTB) and 248 healthy controls (HCs) for CCL2-2518 A>G and -362 G>C polymorphisms by PCR-RFLP and by melting curve analysis using fluorescence-labeled hybridization fluorescent resonance energy transfer (FRET) probes, respectively, followed by DNA sequencing in a few representative samples. Genotype and allele frequencies were compared by the chi-squared test and crude and Mantel-Haenszel (M-H) odds ratio (OR). OR was calculated using STATA/MP16.1 software. Further, CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-β levels were measured in serum samples of these participants using commercially available kits. Our analysis indicated that the homozygous mutant in both -2518 GG ( OR = 2.07 , p = 0.02 ) and -362 CC ( OR = 1.92 , p = 0.03 ) genotypes was associated with susceptibility to pulmonary TB. Further, heterozygous genotypes -2518AG ( OR = 0.60 , p = 0.003 ) and -362GC ( OR = 0.64 , p = 0.013 ) provide resistance from PTB disease. Haplotype analysis revealed AC haplotype ( p = 0.006 ) to be a risk factor associated with PTB susceptibility. The serum CCL2 level was significantly elevated among participants with -2518 AA genotype compared to -2518 GG genotype. CCL2 level was observed to be positively correlated with IL12p70, IFN-γ and TNF-α, thus suggesting the immunological regulatory role of CCL2 against pulmonary tuberculosis. CCL2-2518 GG and -362 CC genotypes were found to be associated with susceptibility to pulmonary tuberculosis and CCL2-2518AG and CCL2-362GC with resistance from PTB. AC haplotype was found to be a risk factor for PTB in the present study. It may be hypothesized from the findings that -2518G allele could be responsible for lower production of CCL2 which leads to defective Th1 response and makes a host susceptible for pulmonary tuberculosis.


2021 ◽  
Vol 7 (25) ◽  
pp. eabg0470
Author(s):  
Jing Zhou ◽  
Xingli Zhang ◽  
Jiajia Hu ◽  
Rihao Qu ◽  
Zhibin Yu ◽  
...  

N6-methyladenosine (m6A) modification is dynamically regulated by “writer” and “eraser” enzymes. m6A “writers” have been shown to ensure the homeostasis of CD4+ T cells, but the “erasers” functioning in T cells is poorly understood. Here, we reported that m6A eraser AlkB homolog 5 (ALKBH5), but not FTO, maintains the ability of naïve CD4+ T cells to induce adoptive transfer colitis. In addition, T cell–specific ablation of ALKBH5 confers protection against experimental autoimmune encephalomyelitis. During the induced neuroinflammation, ALKBH5 deficiency increased m6A modification on interferon-γ and C-X-C motif chemokine ligand 2 messenger RNA (mRNA), thus decreasing their mRNA stability and protein expression in CD4+ T cells. These modifications resulted in attenuated CD4+ T cell responses and diminished recruitment of neutrophils into the central nervous system. Our findings reveal an unexpected specific role of ALKBH5 as an m6A eraser in controlling the pathogenicity of CD4+ T cells during autoimmunity.


2012 ◽  
Vol 302 (9) ◽  
pp. L933-L940 ◽  
Author(s):  
Jiurong Liang ◽  
Yoosun Jung ◽  
Robert M. Tighe ◽  
Ting Xie ◽  
Ningshan Liu ◽  
...  

CC chemokine ligand-2 (CCL2)/monocyte chemoattractant protein (MCP)-1 expression is upregulated during pulmonary inflammation, and the CCL2-CCR2 axis plays a critical role in leukocyte recruitment and promotion of host defense against infection. The role of CCL2 in mediating macrophage subpopulations in the pathobiology of noninfectious lung injury is unknown. The goal of this study was to examine the role of CCL2 in noninfectious acute lung injury. Our results show that lung-specific overexpression of CCL2 protected mice from bleomycin-induced lung injury, characterized by significantly reduced mortality, reduced neutrophil accumulation, and decreased accumulation of the inflammatory mediators IL-6, CXCL2 (macrophage inflammatory protein-2), and CXCL1 (keratinocyte-derived chemokine). There were dramatic increases in the recruitment of myosin heavy chain (MHC) II IA/IEintCD11cintcells, exudative macrophages, and dendritic cells in Ccl2 transgenic mouse lungs both at baseline and after bleomycin treatment compared with levels in wild-type mice. We further demonstrated that MHCII IA/IEintCD11cintcells engulfed apoptotic cells during acute lung injury. Our data suggested a previously undiscovered role for MHCII IA/IEintCD11cintcells in apoptotic cell clearance and inflammation resolution.


2021 ◽  
Author(s):  
Guixiang Liao ◽  
Zhihong Zhao ◽  
Yuxiang Fu

Abstract Background: CC-chemokine ligand 2 (CCL2) expression as a prognostic factor in digestive system cancers (DSCs) is inconclusive. Methods:Thus, our aim was to summarize the prognostic role of CCL2 in DSCs. Electronic database was carefully searched. Studies focusing on CCL2 expression as a prognostic marker in DSCs were included for analysis. Pooled data for survival outcomes and clinical features were recorded in terms of the hazard ratio (HR) or odds ratio (OR) and the 95% confidence interval (CI).Results: In all,1,458 patients with DSCs from 11 studies were included for analysis.The pooled data revealed that high CCL2 expression group was more easy to occur the presence of distal metastases (OR = 3.83, 95% CI: 1.98–7.38, P < 0.001), severer tumor invasion (OR = 2.38, 95% CI: 1.31–4.34, P = 0.005), and advanced Tumor Nodal Metastasis stages (OR = 2.47, 95% CI: 1.12–5.45, P = 0.02). Moreover, poorer overall survival (HR = 2.09, P < 0.001) were observed in the group with high CCL2 expression. High levels of CCL2 also indicated dismay disease-free survival (HR = 1.87, P = 0.005) .Conclusions: Our findings indicate that CCL2 can serve as a prognostic indicator in DSCs.


2019 ◽  
Vol 229 (4) ◽  
pp. S217
Author(s):  
Michael J. Zobel ◽  
Abigail Zamora ◽  
Grace Asuelime ◽  
Shahab Asgharzadeh ◽  
Eugene S. Kim

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