Progenitor “Mycobacterium canettii” clone responsible for lymph node tuberculosis epidemic, Djibouti.
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ABSTRACT:
SUBMITTER: Blouin Y
PROVIDER: S-EPMC3884719 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Mycobacterium canettii, which has a smooth colony morphology, is the tuberculous organism retaining the most genetic traits from the putative last common ancestor of the rough-morphology Mycobacterium tuberculosis complex. To explore whether M. canettii can infect individuals by the oral route, mice were fed phosphate-buffered saline or 106M. canettii mycobacteria and sacrificed over a 28-day experiment. While no M. canettii was detected in negative controls, M. canettii-infected mice yielded granuloma-like lesions for 4/4 lungs at days 14 and 28 postinoculation (p.i.) and positive PCR detection of M. canettii for 5/8 mesenteric lymph nodes at days 1 and 3 p.i. and 5/6 pooled stools collected from day 1 to day 28 p.i. Smooth M. canettii colonies grew from 68% of lungs and 36% of spleens and cervical lymph nodes but fewer than 20% of axillary lymph nodes, livers, brown fat samples, kidneys, or blood samples throughout the 28-day experiment. Ready translocation in mice after digestive tract challenge demonstrates the potential of ingested M. canettii organisms to relocate to distant organs and lungs. The demonstration of this relocation supports the possibility that populations may be infected by environmental M. canettii.
| S-EPMC5695119 | biostudies-literature
Project description:Tuberculosis (TB) in humans is caused by members of the Mycobacterium tuberculosis complex (MTC). Rapid detection of the MTC is necessary for the timely initiation of antibiotic treatment, while differentiation between members of the complex may be important to guide the appropriate antibiotic treatment and provide epidemiological information. In this study, a multiplex real-time PCR diagnostics assay using novel molecular targets was designed to identify the MTC while simultaneously differentiating between M. tuberculosis and M. canettii. The lepA gene was targeted for the detection of members of the MTC, the wbbl1 gene was used for the differentiation of M. tuberculosis and M. canettii from the remainder of the complex, and a unique region of the M. canettii genome, a possible novel region of difference (RD), was targeted for the specific identification of M. canettii. The multiplex real-time PCR assay was tested using 125 bacterial strains (64 MTC isolates, 44 nontuberculosis mycobacteria [NTM], and 17 other bacteria). The assay was determined to be 100% specific for the mycobacteria tested. Limits of detection of 2.2, 2.17, and 0.73 cell equivalents were determined for M. tuberculosis/M. canettii, the MTC, and M. canettii, respectively, using probit regression analysis. Further validation of this diagnostics assay, using clinical samples, should demonstrate its potential for the rapid, accurate, and sensitive diagnosis of TB caused by M. tuberculosis, M. canettii, and the other members of the MTC.
| S-EPMC3043491 | biostudies-literature
Project description:Adipose tissues were shown to host Mycobacterium tuberculosis which is persisting inside mature adipocytes. It remains unknown whether this holds true for Mycobacterium canettii, a rare representative of the M. tuberculosis complex responsible for lymphatic and pulmonary tuberculosis. Here, we infected primary murine white and brown pre-adipocytes and murine 3T3-L1 pre-adipocytes and mature adipocytes with M. canettii and M. tuberculosis as a positive control. Both mycobacteria were able to infect 18-22% of challenged primary murine pre-adipocytes; and to replicate within these cells during a 7-day experiment with the intracellular inoculums being significantly higher in brown than in white pre-adipocytes for M. canettii (p = 0.02) and M. tuberculosis (p = 0.03). Further in-vitro infection of 3T3-L1 mature adipocytes yielded 9% of infected cells by M. canettii and 17% of infected cells by M. tuberculosis (p = 0.001). Interestingly, M. canettii replicated and accumulated intra-cytosolic lipid inclusions within mature adipocytes over a 12-day experiment; while M. tuberculosis stopped replicating at day 3 post-infection. These results indicate that brown pre-adipocytes could be one of the potential targets for M. tuberculosis complex mycobacteria; and illustrate differential outcome of M. tuberculosis complex mycobacteria into adipose tissues. While white adipose tissue is an unlikely sanctuary for M. canettii, it is still an open question whether M. canettii and M. tuberculosis could persist in brown adipose tissues.
| S-EPMC5434109 | biostudies-literature
Project description:Using 894 phylogenetically diverse genomes of the Mycobacterium tuberculosis complex (MTBC), we simulated in silico the ability of the Hain Lifescience GenoType MTBC assay to differentiate the causative agents of tuberculosis. Here, we propose a revised interpretation of this assay to reflect its strengths (e.g., it can distinguish some strains of Mycobacterium canettii and variants of Mycobacterium bovis that are not intrinsically resistant to pyrazinamide) and limitations (e.g., Mycobacterium orygis cannot be differentiated from Mycobacterium africanum).
| S-EPMC6535525 | biostudies-literature
Project description:The onset of the adaptive immune response to Mycobacterium tuberculosis is delayed compared with that of other infections or immunization, and allows the bacterial population in the lungs to expand markedly during the preimmune phase of infection. We used adoptive transfer of M. tuberculosis Ag85B-specific CD4(+) T cells to determine that the delayed adaptive response is caused by a delay in initial activation of CD4(+) T cells, which occurs earliest in the local lung-draining mediastinal lymph node. We also found that initial activation of Ag85B-specific T cells depends on production of antigen by bacteria in the lymph node, despite the presence of 100-fold more bacteria in the lungs. Although dendritic cells have been found to transport M. tuberculosis from the lungs to the local lymph node, airway administration of LPS did not accelerate transport of bacteria to the lymph node and did not accelerate activation of Ag85B-specific T cells. These results indicate that delayed initial activation of CD4(+) T cells in tuberculosis is caused by the presence of the bacteria in a compartment that cannot be mobilized from the lungs to the lymph node, where initial T cell activation occurs.
| S-EPMC2234384 | biostudies-literature
Project description:A small number of high-burden countries account for the majority of tuberculosis cases worldwide. Detailed data are lacking from these regions. To explore the evolutionary history of Mycobacterium tuberculosis in China-the country with the third highest tuberculosis burden-we analysed a countrywide collection of 4,578 isolates. Little genetic diversity was detected, with 99.4% of the bacterial population belonging to lineage 2 and three sublineages of lineage 4. The deeply rooted phylogenetic positions and geographic restriction of these four genotypes indicate that their populations expanded in situ following a small number of introductions to China. Coalescent analyses suggest that these bacterial subpopulations emerged in China around 1,000 years ago, and expanded in parallel from the twelfth century onwards, and that the whole population peaked in the late eighteenth century. More recently, sublineage L2.3, which is indigenous to China and exhibited relatively high transmissibility and extensive global dissemination, came to dominate the population dynamics of M. tuberculosis in China. Our results indicate that historical expansion of four M. tuberculosis strains shaped the current tuberculosis epidemic in China, and highlight the long-term genetic continuity of the indigenous M. tuberculosis population.
| S-EPMC6295914 | biostudies-literature
Project description:Lymph node tuberculosis (LNTB) is characterized by the enhanced baseline and antigen-specific production of type 1/17 cytokines and reduced baseline and antigen-specific production of interleukin (IL)-1β and IL-18 at the site of infection when compared with peripheral blood. However, the cytokine profile in the lymph nodes (LNs) of Mycobacterium tuberculosis culture-positive LNTB (LNTB+) and negative LNTB (LNTB-) has not been examined. To address this, we have examined the baseline and mycobacterial antigen-stimulated cytokine levels of type 1 (interferon gamma [IFNγ], tumor necrosis factor alpha [TNFα], IL-2), type 2 (IL-4, IL-5, and IL-13), type 17 (IL-17A, IL-17F, and IL-22), pro-inflammatory (IL-1α, IL-1β, IL-18, and granulocyte macrophage colony-stimulating factor [GM-CSF]), and regulatory cytokines (IL-10, transforming growth factor beta [TGF-β]) cytokines in the LN culture supernatants of LNTB+ and LNTB- individuals. We have observed significantly enhanced baseline levels of IL-13 and IL-10 and significantly reduced baseline levels of IL-4 and GM-CSF in LNTB+ individuals compared with LNTB- individuals. By contrast, we have observed significantly enhanced levels of type 1 (IFNγ, TNFα, and IL-2), type 17 (IL-17F and IL-22), and pro-inflammatory (IL-1α and GM-CSF) cytokines and significantly reduced levels of TGFβ in response to purified protein derivative, early secreted antigen-6, and culture filtrate protein-10 antigens in LNTB+ compared with LNTB- individuals. On phorbol 12-myristate 13-acetate/ionomycin stimulation, no significant difference was observed for any of the cytokines examined. Thus, our study revealed several interesting differences in the cytokine profiles of mycobacterial antigen-stimulated LN cultures in LNTB+ and LNTB- individuals. Therefore, we suggest the presence of mycobacteria plays a significant role in driving the cytokine response at the site of infection in LNTB.
| S-EPMC6553923 | biostudies-literature
Project description:BackgroundThis study examined potential risk factors of lymph node tuberculosis (LNTB), including phylogenetic lineages of Mycobacterium tuberculosis (MTB), in comparison to pulmonary tuberculosis (PTB) in a setting with an ethnically diverse population.MethodsWe conducted a case-control study at a major tuberculosis clinic in Sydney, Australia, which included all patients with peripheral LNTB seen at the clinic between 2000 and 2012. Controls were randomly selected patients with PTB seen at the same clinic during the study period. Epidemiological data were extracted from the hospital electronic database and medical records. Associations between LNTB and age, sex, ethnicity, comorbidities and phylogenetic lineages of MTB in comparison to PTB were examined using logistic regression in univariate and multivariate analyses.ResultsThere were 212 cases with LNTB and 424 randomly selected controls with PTB. Among patients with LNTB, 74% were female and the mean age (standard deviation, SD) was 42 (16) years. Among patients with PTB, 43% were female and the mean age was 44 (22) years. Females, 45 to 64-year-olds and Southern Asians had an increased risk for LNTB (OR 3.13, 95% CI 2.10-4.67; OR 2.50, 95% CI 1.29-4.84; OR 3.95, 95% CI 1.54-10.12 respectively). Patients with diabetes were at a higher risk of PTB (OR 0.40, 95% CI 0.19 - 0.83 for LNTB). A subset analysis showed that patients infected with the East African Indian strain of MTB were more likely to develop LNTB (OR 10.07, 95% CI 2.37-42.77).ConclusionsAn increased risk for LNTB (but still lower rates than for PTB) was found among females, people aged 45 to 64 years and people born in Southern Asia. An increased risk for PTB was found among patients with diabetes. The East African Indian strain of MTB was significantly associated with a higher likelihood of LNTB compared to other MTB strains.
| S-EPMC4503442 | biostudies-literature
Project description:Lymph nodes are important peripheral immune organs in which numerous important immune responses occur. During the process of lymphatic metastasis, lymph nodes are also sites through which tumor cells must pass. Therefore, it is essential to develop a drug delivery system that can specifically transfer immunostimulatory medicine into lymph nodes to block lymphatic metastasis. Here, we developed a nucleic acid drug delivery system containing cationic agarose (C-agarose) and CpG oligodeoxynucleotides. C-agarose has a high affinity for Siglec-1 on the surface of lymph node sinus macrophages, which have a high specificity for targeting lymph nodes. Subcutaneous implantation of C-agarose+CpG gel caused the accumulation of CpG in the lymph node sinus macrophages and generated antitumor immune responses in the lymph node. C-agarose+CpG gel treatment decreased the metastasis size in the tumor-draining lymph node (TDLN) and lung metastatic nodules and suppressed tumor growth in both a mouse 4T1 breast cancer model and a B16F10 melanoma model. On this basis, this study proposes a nonsurgical invasive lymph node targeting immunotherapy concept that may provide a new approach for antitumor metastasis.
| S-EPMC6529739 | biostudies-literature
Project description:Recruiting large numbers of naïve lymphocytes to lymph nodes is critical for mounting an effective adaptive immune response. While most naïve lymphocytes utilize homing molecule L-selectin to enter lymph nodes, some circulating cells can traffic to the lung-draining mediastinal lymph node (mLN) through lymphatics via the intermediate organ, lung. However, whether this alternative trafficking mechanism operates in infection and contributes to T cell priming are unknown. We report that in pulmonary Mycobacterium tuberculosis-infected mice, homing of circulating lymphocytes to the mLN is significantly less efficient than to non-draining lymph node. CD62L blockade only partially reduced the homing of naïve T lymphocytes, consistent with L-selectin-independent routing of naïve lymphocytes to the site. We further demonstrated that lymphatic vessels in infected mLN expanded significantly and inhibiting lymphangiogenesis with a vascular endothelial growth factor receptor 3 kinase inhibitor reduced the recruitment of intravenously injected naïve lymphocytes to the mLN. Finally, mycobacterium-specific T cells entering via the L-selectin-independent route were readily activated in the mLN. Our study suggests that both L-selectin-dependent and -independent pathways contribute to naïve lymphocyte entry into mLN during M. tuberculosis infection and the latter pathway may represent an important mechanism for orchestrating host defence in the lungs.
| S-EPMC10321623 | biostudies-literature