ABSTRACT
Analysis of receptor-ligand interactions in the context of diseases necessitates to understand how HLA-KIR genotypes function in diseases. Although CD56+ lymphocytes are derived from multiple lineages, they share a functional association with immunosurviellance and antimicrobial responses. The present study aimed to determine whether KIR phenotype in CD56 lymphocytes and corresponding HLA-class 1 ligands are associated with multidrug resistance tuberculosis (MDR-TB). We compared the frequencies of HLA-C and HLA-BW4 genes, the expression of KIRs 2DL1/2DS1, 2DL2/2DL3, 3DL1, and 2DS4 and the combinations of HLA/KIR in 32 Nifamycin and Isoniazid-resistant TB with those in 68 drug non resistant (NR) sputum smear positive pulmonary TB patients. PCR-SSP and flow cytometry were performed for HLA and KIRs typing, respectively. We showed no significant differences between inhibitory or activating KIRs as well as HLA ligands in MDR TB patients compared with NR-TB . The combinations of inhibitory KIR-HLA ligands in MDR-TB were much more prevalent, but not statistically significant than in NR patients (p=0.07). The frequency of MDR patients with all HLA-C and HLA-BW4 ligands was higher than NR-TB (p<0.009). Conversely, the percentage of MDR patients having only one kind of HLA gene was significantly lower than NR-TB (p<0.01). We conclude that the expression of inhibitory KIRs with corresponding HLA ligands genes, and/or co-existence of three HLA class 1 ligands for inhibitory KIRs may be associated with drug resistance in pulmonary tuberculosis.
Subject(s)
Genetic Predisposition to Disease/genetics , HLA Antigens/genetics , Killer Cells, Natural/immunology , Receptors, KIR/genetics , Tuberculosis, Multidrug-Resistant/genetics , CD56 Antigen/immunology , CD56 Antigen/metabolism , Flow Cytometry , HLA Antigens/immunology , Humans , Killer Cells, Natural/metabolism , Ligands , Natural Killer T-Cells/immunology , Natural Killer T-Cells/metabolism , Receptors, KIR/biosynthesis , Receptors, KIR/immunology , Tuberculosis, Multidrug-Resistant/immunology , Tuberculosis, Multidrug-Resistant/metabolismABSTRACT
BACKGROUND: Protective immune responses induced in the majority of people infected with Mycobacterium tuberculosis enable them to control TB infection. OBJECTIVE: The aim of this study was to investigate CD56 and CD16 positive peripheral blood mononuclear cells (PBMCs) and leukocyte subsets from multi-drug resistant pulmonary tuberculosis (MDR-TB), and compare them with nonresistant (NR) TB patients and healthy controls. METHODS: 13 MDR-tuberculosis patients, 20 NR-TB individuals and 40 healthy subjects were included. Peripheral blood mononuclear cells were double stained with fluorochrome conjugated antibodies against CD56 and CD16 cell surface markers. The phenotype of positive cells was then analyzed by flow cytometry and the percentages of CD56+ CD16+, CD56- CD16+, CD56dimCD16+/-, and CD56brightCD16+/- subsets were calculated. RESULTS: There was a significant decline in the percentage of CD56+CD16+ lymphocytes in both MDR and NR-TB patients compared with healthy controls. We also observed lower proportions of CD56dim/brightCD16+ in addition to higher percentages of CD56dim/brightCD16- subsets in all TB patients (p<0.05). In MDR-TB, our findings demonstrated a distinct phenotypic feature with increased levels of CD56brightCD16- in comparison with both NR-TB and healthy subjects. CONCLUSION: Considering the function of CD56/CD16 expressing cells in TB, we suggest that phenotypic characteristics of PBMCs in MDR-TB may correlate with their status of drug resistance and probably with their high mortality rates.