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 (sputum smear-negative), treatment-naïve patients, mean age 32 ± 12.43 years; 28 males and 12 females and studied their peripheral blood (PBL) and bronchoalveolar lavage (BAL) fluid. Of 40 patients, BAL fluid from 10 patients was collected by using fibre-optic bronchoscope. In 4 patients, BAL was collected from both normal as well as diseased lung. Their BAL fluids were subjected to confirm TB using AFB, BACTEC/LJ media and PCR methods. Patients were HIV-negative with parenchymal-lesions on chest radiograph/computerized tomography. Diabetes mellitus, malignancy, pregnancy and corticosteroid therapy were excluded. Immunophenotyping and antigen specific intracellular cytokines were performed by using flow cytometry and analysed by flowjo software.
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 = 10). Increased frequency of CXCR3+CCR5+ T cells (P = 0.02), CXCR3+ T cells (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=4). 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+ Th1cells with the ability to produce inflammatory cytokines and CD11ahigh Th1 cells which play an important role in the recruitment of these Th1cells, 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; Th1 cells