MCP-1 -362C was associated with resistance to TB in the case-control collection (OR 0.83, P(corr) = 0.00017) and in the affected families (OR 0.7, P(corr) = 0.004).
Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied.
CCR2 V64I (G/A), monocyte chemoattractant protein-1 (MCP-1) -2518 A/G, stromal cell derived factor-1alpha; (SDF-1alpha) 3'UTR G/A and DC-SIGN gene polymorphisms were studied by polymerase chain reaction based methods in HIV-1 infected patients without TB (n=151), with pulmonary TB (PTB) (n=81) and extrapulmonary TB (n=31), 155 PTB patients without HIV and 206 healthy controls.
Genetic association meta-analysis: a new classification to assess ethnicity using the association of MCP-1 -2518 polymorphism and tuberculosis susceptibility as a model.
Genomic DNA from patients with active TB (168 cases of pulmonary TB and 55 cases of extrapulmonary TB) and ethnically controls (150 cases) was genotyped for the MCP-1-2518 A/G SNP by polymerase chain reaction fragment length polymorphism (PCR-RFLP).
Given the roles played by IFN-gamma and VDR in facilitating macrophage containment of M. tuberculosis and the opposing role of MCP-1 and IL-6, the observed allelic variation by ethnicity may in part contribute to the high rates of tuberculosis among the Dené.
Higher mRNA expression levels of inducible nitric oxide synthase, C-C motif chemokine ligand 2 and IL-12 were observed in macrophages from all in-contact cattle than in macrophages from their TB-infected counterparts, which expressed more tumour necrosis factor-α; however, the differences were not statistically significant owing to individual variation.
Human alveolar macrophages produced CCL2 in a PGL-dependent fashion following infection, arguing for the potential of PGL-blocking interventions or PGL-targeting vaccine strategies in the prevention of tuberculosis.VIDEO ABSTRACT.
In a Ghanaian tuberculosis (TB) case-control study group, associations of the MCP1 -362C and the MCP1 -2581G alleles with resistance to TB were recently described.
In addition, nominal significance was observed for an association between TB incidence and both the eight paired genotypes in the overall patient cohort (0.017 < p < 0.05) and the CCL2-2518A/G polymorphism among males (dominant model, OR = 0.55, p = 0.041; log-additive model, OR = 0.57, p = 0.018).
In addition, the DEGs, such as CD14 molecule (CD14) and chemokine (C-C motif) ligand 2 (CCL2), were enriched mostly in the pathways related to tuberculosis, phagosome and NF-kappa B signaling pathway.
In conclusion, these results indicate a specific role for both p38 MAPK and IL-4 in ESAT-6-induced MCP-1 production by macrophages and suggest a pathway with significance in tuberculosis pathogenesis.
In the subsequent validation cohort analysis, we identified that the AUC of MCP-1 in diagnosing ATB and differentiating ATB from LTBI were 0.97 and 0.89, respectively, which was generally consistent with the results of the discovery cohort.
In this study, pleural fluid from patients with tuberculosis contained significantly (P<.001) more biologically active MIP-1alpha and MCP-1 (C-C cytokines) than did effusions from patients with congestive heart failure.
Our findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which inhibits production of IL-12p40 in response to M. tuberculosis and increases the likelihood that M. tuberculosis infection will progress to active pulmonary tuberculosis.
Peripheral blood mononuclear cells obtained from 21 pulmonary tuberculosis (PTB) patients and 24 healthy controls (HCs) were cultured for 48 h with culture filtrate antigen (CFA) of Mycobacterium tuberculosis with or without vitamin D(3) at a concentration 1 × 10(-7)M. The relative mRNA expression of monocyte chemoattractant protein-1 (MCP-1, CCL2), macrophage inflammatory protein-1α (MIP-1α, CCL3), macrophage inflammatory protein-1β (MIP-1β, CCL4), and regulated upon-activation, normal T cell-expressed and secreted (RANTES, CCL5) and IFN-γ inducible protein-10 (IP-10, CXCL10) chemokines were estimated from 48 h old macrophages using real-time polymerase chain reaction (RT-PCR).
The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of monocytes to M. tuberculosis infection sites, and previous studies have reported that genetic variants in MCP1 are associated with differential susceptibility to pulmonary tuberculosis (PTB).
The present study found an association of the CCL2 tag SNP rs4586 C allele and pediatric TB disease in males, suggesting that gender may affect the susceptibility to TB even in children.
The results revealed an association between the MCP-1-2518A/G polymorphism and human TB susceptibility under a recessive model (GG vs GA+AA), dominant model (GG+GA vs AA), and homozygote comparison (GG vs AA) model for the entire database.