Regulatory T cells: Friends or foe in human Mycobacterium leprae infection?

Chaves, Ana Cristina; Ribeiro-Junior, Atvaldo F.; Lyon, Sandra; Medeiros, Nayara I.; Cassirer-Costa, Fábio; Paula, Karina S.; Alecrim, Edilamar Silva de; Menezes, C. A. S.; Correa-Oliveira, Rodrigo; Rocha, Manoel Otávio Costa; Gomes, Juliana de Assis Silva

doi:10.1016/j.imbio.2017.11.002

Cited by 10 publications

(5 citation statements)

References 37 publications

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“…In contrast, in paucibacillary leprosy patients, Tregs express elevated levels of CD95L, possibly related to apoptosis pathways that reduce Tregs. These findings indicate distinct suppression mechanisms and inefficient inflammation regula-tion, potentially contributing to the persistence of multibacillary leprosy during M. leprae infection [24,25].…”

Section: Discussionmentioning

confidence: 93%

Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?

Rembao-Bojórquez,

Sánchez-Garibay,

Salinas-Lara

et al. 2023

Pathogens

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Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.

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Section: Discussionmentioning

confidence: 93%

Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?

Rembao-Bojórquez,

Sánchez-Garibay,

Salinas-Lara

et al. 2023

Pathogens

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“…Anergy in leprosy has been linked to the emergency of regulatory T cell activity. [12][13][14] Anergy nullify the immunologic capacity of the patient to cope with the bacillus. Although there is a lot of information on the mechanisms of immunity in leprosy, anergy is still a phenomenon poorly understood (Rojas-Espinosa [1]) Murine leprosy, is a disease that traverse all forms of leprosy from the tuberculoid-like to the lepromatous-like disease (Rojas-Espinosa [5]) Murine leprosy is an excellent animal model for studying the development of anergy that appears in the middle stages of the infection.…”

Section: Discussionmentioning

confidence: 99%

"Regulatory T Cells (Treg) Participate in the Development of Anergy in Murine Leprosy"

Espinosa

2023

BJSTR

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Specific loss of cell-mediated immunity to Mycobacterium leprae, is a characteristic feature of human lepromatous leprosy. This phenomenon is called cellular anergy and it is considered the reason for the disease progression. It is not clear the reason for anergy in human leprosy, but several experimentalbased explanations have been proposed. One such explanation is the excess of suppression exerted by regulatory T cells (Treg). In murine leprosy, caused by Mycobacterium lepraemurium, cellular anergy is also observed and the model offers the opportunity to further explore the phenomenon vertically, in the same animal because of the availability of syngeneic strains, and during the whole time of infection. Syngeneic Balb/c mice were inoculated with MLM, and the evolution of the infection was monitored over 4 months based on diverse parameters: body weight, splenomegaly and hepatomegaly, presence of bacilli, and presence of CD4+CD25+Tbet and CD4+CD25+FoxP3 cells. It was found, by flow cell cytometry, that the first immune response in the infected animals reflected the activity of Th1 (Tbet+) cells and this response was then substituted by a predominant T-FoxP3 response, thus suggesting that CD4+CD25+FoxP3 cells play a role in the development of anergy in the malignant form of murine leprosy.

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“…Transforming growth factor-β also mediates the generation of peripheral T cells (p), Th17, Th9, and Tfh, and tissue-resident T cells that generally play an important role in maintaining peripheral tolerance and driving the immune response to pathogens. [31][32][33][34] The increase in systemic proinflammatory mediators due to M. leprae infection also causes macrophages to differentiate and produce IL-10 and TGF-β cytokines. 15 This study has been able to prove that serum TGF-β levels have a moderate positive correlation with IgM anti-PGL-1 levels in household contacts of multibacillary leprosy patients, which means that serum TGF-β can be used as an alternative marker in subclinical leprosy, with a sensitivity of 76.3% and a specificity of 73.5% with a cut-off value of 166.5 pg/mL.…”

Section: Auc: 775%mentioning

confidence: 99%

Levels of TGF- Serum Positively Correlated with Levels of IgM Anti PGL-1 In Household Contacts of Multibacillary Leprosy Patients

Primasari,

Rusyati,

Karmila

et al. 2023

J Biomedika dan Kesehat

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Background Leprosy is a chronic progressive infectious disease. Phenolic glycolipid-1 (PGL-1) is an antigen of Mycobacterium leprae, which can trigger the host’s antibody response. Transforming growth factorβ (TGF-β) plays an immunosuppressive role when the host is exposed to PGL-1 antigen or other M. leprae antigens. This study aims to determine the correlation of TGF-β levels with IgM anti-PGL-1 levels in patients with multibacillary leprosy household contacts. Methods Observational analytical study with a cross-sectional approach. The study subjects consisted of 48 household contact subjects and 24 non-household contact subjects aged 15-65 years old who were selected by consecutive sampling based on inclusion and exclusion criteria. 3 mL of venous blood samples were taken and then examined for IgM anti-PGL-1 and TGF-β with the ELISA kit. Data analysis was carried out using SPSS version 23, and a p-value <0.05 was significant. Results The mean level of IgM anti-PGL-1 in the household contact group was 685.46 ± 290.79 u/mL, while in the non-household contact group was 345.50 ± 206.58 u/mL. The mean TGF-β level in household contact groups was 256.69 ± 127.41 pg/mL, while in the non-household contact group was 144.85 ± 36.73 pg/mL (p<0.001). This study found a moderate positive relationship (r=0.450, p<0.001) between levels of TGF-β and IgM anti-PGL-1 household contacts and non-household contacts group. Conclusions The mean level of IgM anti-PGL-1 and TGF-β in household contacts is higher than in non-household contacts, with a significant difference. There is a moderate positive significant relationship between levels of TGF-β and IgM anti-PGL-1 household contacts and non-household contacts group.

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Regulatory T cells: Friends or foe in human Mycobacterium leprae infection?

Cited by 10 publications

References 37 publications

Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?

Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?

"Regulatory T Cells (Treg) Participate in the Development of Anergy in Murine Leprosy"

Levels of TGF- Serum Positively Correlated with Levels of IgM Anti PGL-1 In Household Contacts of Multibacillary Leprosy Patients

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