Role of CXCR3+CCR5+ Th1 cells in pulmonary tuberculosis patients: At pathogenic site

Abstract

Objective: Tuberculosis (TB) still remains a major global public health problem followed by drug-resistant TB. Understanding of deeper immunopathogenesis into the pathogen–host interactions is required so that it can be translated into effective tools at a public health level. Methods: We recruited 40 pulmonary TB (PTB, sputum smear-negative) patients and studied their peripheral blood (PBL) and bronchoalveolar lavage (BAL) fluid. Of 40 patients, BAL fluid from 10 patients was collected from normal lung and diseased lung in the same patients. Immunophenotyping and intracellular cytokines were performed by flow cytometry. Results: We observed a significant increased expression of CXCR3+CCR5+T-cells (P = 0.002), CXCR3+ T-cells (P = 0.002), CCR5+ T-cells (P = 0.002), CXCR3+CD11ahigh T-cells (P = 0.002), and CCR5+CD11ahigh T-cells (P = 0.002) in BAL (n = 10) over PBL (n = 40). Increased frequency of CXCR3+CCR5+ T-cells (P = 0.02), CXCR3+ (P = 0.034), CCR5+T-cells (P = 0.039), CXCR3+CD11ahigh T-cells (P = 0.05), and CCR5+CD11ahigh T-cells (P = 0.05) was also observed in BAL of disease lung as compared to normal lung (n = 10). There was a significant decrease of inflammatory cytokine (P = 0.028) in the interferon-gamma level, whereas interleukin-4 level was significantly increased (P = 0.028) in BAL as compared to PBL. Conclusion: We conclude that in spite of significant enrichment of CXCR3+CCR5+ Th1-cells with the ability to produce inflammatory cytokines and CD11ahigh T-cells which play an important role in the recruitment of these T-cells, they are not able to control the TB infection. Therefore, our data provide insight into the functionality of effector T-cells at the disease site.

Keywords

• CXCR3
• CCR5
• pulmonary tuberculosis
• tuberculosis
• T-cells