Regulatory role of CCL5 (rs2280789) and CXCL10 (rs56061981) gene polymorphisms on intracellular CCL5 and CXCL10 expression in pulmonary tuberculosis.
Genetic variations in chemokine genes influence the chemoattractive properties of T cells which may be associated with outcome of infections. In present study, we have investigated the regulatory role played by In1.1T/C (rs2280789) polymorphism of CCL5 and -135G/A (rs56061981) polymorphism of CXCL10 gene on intracellular CCL5 and CXCL10 expression in T cells. Whole blood cell cultures were stimulated with culture filtrate antigen (CFA) and infected with live M. tuberculosis were used for intracellular CCL5 and CXCL10 expression using flow cytometry. Genotyping was performed using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP). Significantly higher expression of CCL5 expressing CD3+ and CD3+ CD8+ T cells were observed in HCs with In1.1TT genotype compared to C allele carrier (TT+TC) under unstimulated and CFA induced cultures (p<0.05). In -135G/A (rs56061981) polymorphism, PTB patients with GG genotype showed a significantly decreased expression of CD3+ CXCL10+ and CD3+ CD4+ CXCL10+ T cells compared to A allele carrier (GA+AA) under unstimulated, CFA induced and M. tuberculosis infected cultures (P<0.05). The present study suggest that TT genotype of CCL5 In1.1T/C (rs2280789) polymorphism play an important role to increased CCL5 expression in T cell which may enhanced Th1 immunity and help in protection against tuberculosis. The study also suggests GG genotype of CXCL10 -135G/A (rs56061981) polymorphism decreased CXCL10 expression in T cells which may have defective recruitment of mononuclear cells at the site of infection as well granuloma formation and in turn contribute to progression of TB.
Department of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, MLC 2021 3333 Burnet Avenue, Cincinnati, OH 45229, USA; Department of Immunology, National Institute for Research in Tuberculosis (Formerly Tuberculosis Research Centre), Indian Council of Medical Research, Chennai 600 031, India. Electronic address: mkubiotech@gmail.com.
Brijendra
B
Singh
Department of Immunology, National Institute for Research in Tuberculosis (Formerly Tuberculosis Research Centre), Indian Council of Medical Research, Chennai 600 031, India.
Selvaraj
S
Anbalagan
Department of Immunology, National Institute for Research in Tuberculosis (Formerly Tuberculosis Research Centre), Indian Council of Medical Research, Chennai 600 031, India.
Paramasivam
P
Selvaraj
D000328:Adult; D002465:Cell Movement / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics*; D054357:Chemokine CXCL10 / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006099:Granuloma / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000235:genetics*
C483024:CCL5 protein, human; C114753:CXCL10 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10