The role of Mycobacterium tuberculosis lineages on lung tissue damage and TNF-α level among tuberculosis patients, Indonesia

Abstract

Background: Mycobacterium tuberculosis (MTB) is divided into ancient and modern lineage. Both lineages have different virulence property and therefore associated with different immune responses and disease severity in tuberculosis (TB) patients. The aim of this study was to determine the association between MTB lineages and the level of tumor necrosis factor alpha (TNF-α), and lung tissue damage among Indonesian TB patients. Methods: Thirty new and active TB patients were recruited randomly from Dr. Soewandhie Hospital, Surabaya, Indonesia. MTB isolates were isolated from bronchoalveolar lavage fluid (BALF) and their lineages were determined by primer-specific PCR targeting TbD1 and RD9 region gene. The degree of lung tissue damage was assessed and classified using NICE Scoring System and TNF-α level of BALF was measured by ELISA. Results: MTB were detected in all patients in which 17 and 13 isolates were classified as modern and ancient lineage, respectively. Modern lineage was associated with the degree of lung damage (odds ratio [OR]: 3.97; 95% CI: 1.57-6.37), p < 0.001). This lineage was also associated with high TNF-α level (OR: 2.06; 95% CI: 1.31-47.00, p=0.026). In addition, the level of TNF-α was higher in severe compared to mild lung damage cases (p = 0.001). Conclusion: Modern lineage is likely associated with high TNF-α level and increases the risk of having severe lung damage three times among TB patients from Indonesia. Therefore, laboratory test to determine MTB lineages might crucial to be integrated in National Tuberculosis Control Program in the country.

The Usefulness of Bronchoscopy in the Diagnosis of Mycobacterium tuberculosis Complex Species Infection

“…Furthermore, this study showed that hyperemic, edema, ulcerative, and fibrostenosis types were mostly presented in M. tuberculosis strain Beijing than M. bovis strain BCG infection (Table 3). This may be due to differences in virulence between MTBC species and M. tuberculosis Beijing strain has high virulence such as the ability to induce lung parenchymal severe damage with extensive necrotizing pneumonia [30], [31]. An in vitro study showed that there are differences in the ability to induce pulmonary cell death and to release various cellular components as harmful signals in macrophages infected by the M tuberculosis Beijing strain [32].…”

Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3

“…Despite the strongly clonal population structure of the MTBC, evidence is accumulating on phylogenetically associated biomedical consequences of the diversity of the pathogen. This genomic diversity can potentially lead to different pathobiological features, such as disease severity [ 28 , 29 ] and dormancy [ 28 , 30 , 31 ], or can affect treatment outcomes [ 32 ], bacterial fitness [ 33 ], or resistance levels to anti-TB drugs [ 34 ]. (Phylo)genetic determinants of such pathobiological differences have recently been pointed out.…”

Characterisation of secretome-based immune responses of human leukocytes infected with variousMycobacterium tuberculosislineages

“…The lack of the TbD1 genome region in the more recent lineages (EA, EAI, EuA) is associated with a decrease of immune response level compared to the ancestral lineage (IO) ( Portevin et al., 2011 ). Based on patient serum analysis and macrophage culture experiments, the IO lineage of Mtb induces higher levels of immune activation compared to the EA and EuA lineages ( Amin et al., 2019 ; Portevin et al., 2011 ). Our study using primary cells in culture has also found that immune responses to the IO lineage differ from those to other lineages.…”