Analysis of apoptosis and Bcl-2 expression in polar forms of leprosy

Souza, Vânia Niéto Brito de; Nogueira, Maria Esther Salles; Belone, Andréa de Faria Fernandes; Soares, Cléverson Teixeira

doi:10.1111/j.1574-695x.2010.00746.x

Cited by 14 publications

(12 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In L-lep lesions, BCL2 was upregulated, as previously described [66]. Studies with the intracellular pathogen Coxiella burnetti have demonstrated that this pathogen may modulate autophagy as well as apoptosis pathways through BECN1/BCL2 interplay modification to generate a persistent bacterial infection in the host cells [67].…”

Section: Discussionmentioning

confidence: 77%

Autophagy Is an Innate Mechanism Associated with Leprosy Polarization

et al. 2017

View full text Add to dashboard Cite

Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. Levels of IFN-γ are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. IFN-γ primes macrophages for inflammatory activation and induces the autophagy antimicrobial mechanism. The involvement of autophagy in the immune response against Mycobacterium leprae remains unexplored. Here, we demonstrated by different autophagic assays that LC3-positive autophagosomes were predominantly observed in T-lep when compared with L-lep lesions and skin-derived macrophages. Accumulation of the autophagic receptors SQSTM1/p62 and NBR1, expression of lysosomal antimicrobial peptides and colocalization analysis of autolysosomes revealed an impairment of the autophagic flux in L-lep cells, which was restored by IFN-γ or rapamycin treatment. Autophagy PCR array gene-expression analysis revealed a significantly upregulation of autophagy genes (BECN1, GPSM3, ATG14, APOL1, and TPR) in T-lep cells. Furthermore, an upregulation of autophagy genes (TPR, GFI1B and GNAI3) as well as LC3 levels was observed in cells of L-lep patients that developed type 1 reaction (T1R) episodes, an acute inflammatory condition associated with increased IFN-γ levels. Finally, we observed increased BCL2 expression in L-lep cells that could be responsible for the blockage of BECN1-mediated autophagy. In addition, in vitro studies demonstrated that dead, but not live M. leprae can induce autophagy in primary and lineage human monocytes, and that live mycobacteria can reduce the autophagy activation triggered by dead mycobacteria, suggesting that M. leprae may hamper the autophagic machinery as an immune escape mechanism. Together, these results indicate that autophagy is an important innate mechanism associated with the M. leprae control in skin macrophages.

show abstract

Section: Discussionmentioning

confidence: 77%

Autophagy Is an Innate Mechanism Associated with Leprosy Polarization

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The role of apoptosis during M. leprae infection is not clear, and different research settings have demonstrated both anti- ( 24 , 63 ) and proapoptotic ( 64 , 65 ) features, in addition to possible differences depending on the clinical form of leprosy ( 66 ). BCL2 has been shown to be highly expressed in LL patients ( 66 ), and BCL2 and MCL1 gene are induced by M. leprae on monocytes ( 63 ), while CASP8 activity in LL is decreased ( 67 ). We found several miRNAs controlling apoptosis pathways in LP.…”

Section: Discussionmentioning

confidence: 99%

miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology

Salgado

Pinto²,

Bouth

et al. 2018

Front. Immunol.

View full text Add to dashboard Cite

Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease. Thus, we examined the miRNome of tuberculoid (TT) and lepromatous (LL) patients using both blood and lesional biopsies from classical leprosy patients (LP) who visited the Dr. Marcello Candia Reference Unit in Sanitary Dermatology in the State of Pará and compared them with healthy subjects. Using a set of tools to correlate significantly differentially expressed miRNAs with their gene targets, we identified possible interactions and networks of miRNAs that might be involved in leprosy immunophysiopathology. Using this approach, we showed that the leprosy miRNA profile in blood is distinct from that in lesional skin as well as that four main groups of genes are the targets of leprosy miRNA: (1) recognition and phagocytosis, with activation of immune effector cells, where the immunosuppressant profile of LL and immunoresponsive profile of TT are clearly affected by miRNA expression; (2) apoptosis, with supportive data for an antiapoptotic leprosy profile based on BCL2, MCL1, and CASP8 expression; (3) Schwann cells (SCs), demyelination and epithelial–mesenchymal transition (EMT), supporting a role for different developmental or differentiation gene families, such as Sox, Zeb, and Hox; and (4) loss of sensation and neuropathic pain, revealing that RHOA, ROCK1, SIGMAR1, and aquaporin-1 (AQP1) may be involved in the loss of sensation or leprosy pain, indicating possible new therapeutic targets. Additionally, AQP1 may also be involved in skin dryness and loss of elasticity, which are well known signs of leprosy but with unrecognized physiopathology. In sum, miRNA expression reveals new aspects of leprosy immunophysiopathology, especially on the regulation of the immune system, apoptosis, SC demyelination, EMT, and neuropathic pain.

show abstract

“…Analysis of skin lesion cells demonstrated that apoptosis is more frequent in tuberculoid and reversal reaction than in lepromatous cells ( 157 – 159 ). Lepromatous cells present increased expression of the antiapoptotic protein Bcl-2, suggesting that the decrease in cell death could contribute for sustains the infection ( 158 ).…”

Section: Manipulation Of Innate Immunity By M Lepraementioning

confidence: 99%

Innate Immune Responses in Leprosy

et al. 2018

View full text Add to dashboard Cite

Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Several studies have clarified the role of various T cell populations in leprosy; however, recent evidences suggest that local innate immune mechanisms are key determinants in driving the disease to its different clinical manifestations. Leprosy is an ideal model to study the immunoregulatory role of innate immune molecules and its interaction with nervous system, which can affect homeostasis and contribute to the development of inflammatory episodes during the course of the disease. Macrophages, dendritic cells, neutrophils, and keratinocytes are the major cell populations studied and the comprehension of the complex networking created by cytokine release, lipid and iron metabolism, as well as antimicrobial effector pathways might provide data that will help in the development of new strategies for leprosy management.

show abstract

Analysis of apoptosis and Bcl-2 expression in polar forms of leprosy

Cited by 14 publications

References 18 publications

Autophagy Is an Innate Mechanism Associated with Leprosy Polarization

Autophagy Is an Innate Mechanism Associated with Leprosy Polarization

miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology

Innate Immune Responses in Leprosy

Contact Info

Product

Resources

About