NFκB activation in cutaneous lesions of leprosy is associated with development of multibacillary infection

Abstract

BackgroundNuclear factor kappa B (NFκB) transcription factors play a central role in controlling the expression of genes involved in inflammatory reactions, proliferation, and survival of human cells. However, the in situ evaluation of NFκB activity in leprosy has not been completed previously. The aim of this study was to determine whether NFκB activity correlates with susceptibility or resistance to Mycobacterium leprae infection in biopsies from skin lesions of 38 patients with the clinical and laboratory diagnosis of leprosy.MethodsThe NFκB activation profile was evaluated in biopsies from skin lesions of 38 patients with the clinical and laboratory diagnosis of leprosy. NFκB activation was evaluated and quantified by Southwestern histochemistry, and its activation index (range, 0–4) was calculated according to the percentage of nuclear positivity by the histochemistry. Activation index >1 was considered representative of activation of NFκB.ResultsFifteen patients (39.5%) demonstrated activated NFκB. Multibacillary leprosy was associated with activated NFκB (54.5%, P=0.028). Borderline leprosy was most strongly associated with NFκB activation (80%), with an odds ratio of 32.7 (P=0.016). These clinical forms are characterized by increased susceptibility to M. leprae and by immunological instability. Activation of NFκB was absent in the granulomas in tuberculoid leprosy, which represents an effective inflammatory reaction pattern against M. leprae.ConclusionThese results indicate that NFκB activation could favor susceptibility and immunological instability to M. leprae infection, potentially by the stimulation of phagocytosis and the regulation of apoptotic mechanisms of infected cells, leading to the proliferation of this intracellular bacillus. Further studies are needed to evaluate if inhibition of NFκB activation in multibacillary leprosy could favor resistance and an effective granulomatous immune response.

Reanalysis and integration of public microarray datasets reveals novel host genes modulated in leprosy

“…Furthermore, enrichment analysis of these genes resulted in several converging ontologies when comparing the results obtained from datasets on human skin biopsies. This approach has strengthened the importance of some previous known pathways, such as: type 1 and 2 interferon pathways [15,56], tumor necrosis factor [57], and NF-kappa B signaling [58,59].…”

Os Efeitos Da Microcorrente E Do Oligoelemento Selênio Nas Disfunções Teciduais Da Face Do Tabagista

“…Outra forma de atuação conhecida da vitamina D é na inibição do fator nuclear kappa B (NF-kB), este que pode favorecer a susceptibilidade imunológica à M. leprae, especialmente à forma multibacilar da hanseníase (TELES et al, 2013;WAMBIER et al, 2014;TONIATO et al, 2015;OLIVEIRA et al, 2017). Estudos sugerem aplicação da terapia com vitamina D em pacientes com asma, para atuação contra a ativação excessiva do NF-kB nas atividades das células musculares lisas das vias aéreas humanas (SONG et al, 2013).…”

Association between SNPs in microRNAs and microRNAs-Machinery Genes with Susceptibility of Leprosy in the Amazon Population

“…This microRNA targets the A20 protein, an inhibitor of the NF-kB pathway, so let-7f expression decreases and A20 increases with the progression of M. tuberculosis infection in mice [56]. Wambier et al, report that PB leprosy patients, who present greater immune reactivity against M. leprae, exhibited less NF-kB activation when compared to MB patients [57].…”