The involvement of endothelial mediators in leprosy

Suvirya

et al. 2021

Dermatologic Therapy

Reactions in leprosy have an immune mediated pathogenesis. While type 1 reactions are delayed hypersensitivity phenomenon, type 2 reactions are immune complex mediated. Key molecules which mediate the immune insult in lepra reactions require evaluation in order to tailor their therapy and prevent disability. The objective of the study was to evaluate expressions of Cyclooxygenase 2 and Vascular Endothelial Growth Factor in skin biopsies from leprosy patients and correlate their expression with presence of either type 1 or type 2 lepra reactions. This was a case control study. Cyclooxygenase 2 and Vascular Endothelial Growth Factor expression in dermal macrophages and vascular endothelium was assessed immunohistochemically. Biopsies from patients with Non-reactive leprosy and healthy controls were used for comparison. SPSS software was used for statistical analysis. A total of 147 skin biopsies were evaluated, including 18 with Type 1 reaction, 39 Type 2 reaction, 81 non-reactive leprosy and 9 healthy controls. Both Cyclooxygenase 2 and Vascular Endothelial Growth Factor expression were significantly higher in type 1 followed by type 2 reaction as compared to controls. These results may guide us regarding use of Cyclooxygenase 2 and Vascular Endothelial Growth Factor inhibitor drugs which may be a major step in treating reactive leprosy patients and preventing nerve damage and disability.

Section: Discussioncontrasting

confidence: 77%

Cyclooxygenase 2 and vascular endothelial growth factor–potential targets to manage lepra reactions: A case‐control study

Suvirya

et al. 2021

Dermatologic Therapy

“…Considering the miRNA profile controlling cell receptors, in addition to FAS gene , we found five other genes related to apoptosis control by miRNA in M. leprae infection: TGFBR1 , involved in TGF-β signaling, a cytokine known to induce tolerance ( 73 , 74 ) with a suppressive potential of Tregs in LL patients ( 75 ); ITGA5 , an α-integrin linked to M. tuberculosis infection of macrophages ( 22 ); VEGFR2 , known to participate in M. tuberculosis dissemination by triggering angiogenesis ( 76 ), while its ligand, VEGFA , has been demonstrated to be expressed in leprosy lesions ( 77 ); PDGFRA , which was shown to be upregulated in SC 27 days after M. leprae infection ( 78 ), and its ligand PDGF , a potential marker for erythema nodosum leprosum ( 79 ); and IGF1R , the receptor of IGF1 , which inhibits macrophage and SC apoptosis upon M. leprae infection, in turn stimulating the production and secretion of IGF1 ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology

Salgado

Pinto²,

Bouth

et al. 2018

Front. Immunol.

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.

“…Previous studies have demonstrated that HIV-1 infection of macrophages prime or induce their polarization toward a proinflammatory phenotype that contributes to the establishment and maintenance of a state of chronic activation that is credited to represent a major determinant of HIV disease progression (36)(37)(38). In the present study, we selected a group of genes previously described as involved in leprosy pathogenesis (3,5,6,(39)(40)(41)(42)(43)(44)(45). Analysis of cell phenotype revealed an increase of anti-inflammatory cell markers in RR/HIV when compared with RR cells.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Polarization in Leprosy–HIV Co-infected Patients

et al. 2020

In HIV-infected individuals, a paradoxical clinical deterioration may occur in preexisting leprosy when highly active antiretroviral therapy (HAART)-associated reversal reaction (RR) develops. Leprosy-HIV co-infected patients during HAART may present a more severe form of the disease (RR/HIV), but the immune mechanisms related to the pathogenesis of leprosy-HIV co-infection remain unknown. Although the adaptive immune responses have been extensively studied in leprosy-HIV co-infected individuals, recent studies have described that innate immune cells may drive the overall immune responses to mycobacterial antigens. Monocytes are critical to the innate immune system and play an important role in several inflammatory conditions associated with chronic infections. In leprosy, different tissue macrophage phenotypes have been associated with the different clinical forms of the disease, but it is not clear how HIV infection modulates the phenotype of innate immune cells (monocytes or macrophages) during leprosy. In the present study, we investigated the phenotype of monocytes and macrophages in leprosy-HIV co-infected individuals, with or without RR. We did not observe differences between the monocyte profiles in the studied groups; however, analysis of gene expression within the skin lesion cells revealed that the RR/HIV group presents a higher expression of macrophage scavenger receptor 1 (MRS1), CD209 molecule (CD209), vascular endothelial growth factor (VEGF), arginase 2 (ARG2), and peroxisome proliferator-activated receptor gamma (PPARG) when compared with the RR group. Our data suggest that different phenotypes of tissue macrophages found in the skin from RR and RR/HIV patients could differentially contribute to the progression of leprosy.