Expression of NLRP3 inflammasome in leprosy indicates immune evasion of Mycobacterium leprae.

BACKGROUND: Leprosy is an infectious-contagious disease caused by Mycobacterium leprae that remain endemic in 105 countries. This neglected disease has a wide range of clinical and histopathological manifestations that are related to the host inflammatory and immune responses. More recently, the inflammasome has assumed a relevant role in the inflammatory response against microbiological agents. However, the involvement of inflammasome in leprosy remains poorly understood. OBJECTIVES: The aim is to associate biomarkers of inflammasome with the different immunopathological forms of leprosy. METHODS: We performed an observational, cross-sectional, and comparative study of the immunophenotypic expression of inflammasome-associated proteins in immunopathological forms of leprosy of 99 skin lesion samples by immunohistochemistry. The intensity and percentage of NLRP3, Caspase-1, Caspases-4/5, interleukin-1ß and interleukin-18 immunoreactivities in the inflammatory infiltrate of skin biopsies were evaluated. FINDINGS: Strong expression of NLRP3 and inflammatory Caspases-4/5 were observed in lepromatous leprosy (lepromatous pole). In addition, were observed low expression of caspase-1, interleukin-1ß, and interleukin-18 in tuberculoid and lepromatous leprosy. The interpolar or borderline form showed immunophenotype predominantly similar to the lepromatous pole. MAIN CONCLUSIONS: Our results demonstrate that the NLRP3 inflammasome is inactive in leprosy, suggesting immune evasion of M. leprae.

Expression of NLRP3 inflammasome in leprosy indicates immune evasion of Mycobacterium leprae

BACKGROUND Leprosy is an infectious-contagious disease caused by Mycobacterium leprae that remain endemic in 105 countries. This neglected disease has a wide range of clinical and histopathological manifestations that are related to the host inflammatory and immune responses. More recently, the inflammasome has assumed a relevant role in the inflammatory response against microbiological agents. However, the involvement of inflammasome in leprosy remains poorly understood. OBJECTIVES The aim is to associate biomarkers of inflammasome with the different immunopathological forms of leprosy. METHODS We performed an observational, cross-sectional, and comparative study of the immunophenotypic expression of inflammasome-associated proteins in immunopathological forms of leprosy of 99 skin lesion samples by immunohistochemistry. The intensity and percentage of NLRP3, Caspase-1, Caspases-4/5, interleukin-1β and interleukin-18 immunoreactivities in the inflammatory infiltrate of skin biopsies were evaluated. FINDINGS Strong expression of NLRP3 and inflammatory Caspases-4/5 were observed in lepromatous leprosy (lepromatous pole). In addition, were observed low expression of caspase-1, interleukin-1β, and interleukin-18 in tuberculoid and lepromatous leprosy. The interpolar or borderline form showed immunophenotype predominantly similar to the lepromatous pole. MAIN CONCLUSIONS Our results demonstrate that the NLRP3 inflammasome is inactive in leprosy, suggesting immune evasion of M. leprae.

Multi-parameter approach to evaluate the timing of memory status after 17DD-YF primary vaccination

Nesta investigação, as técnicas melhoradas por máquina foram aplicadas para trazer insights científicos para identificar um conjunto mínimo de biomarcadores relacionados à memória fenotípica / funcional para o acompanhamento pós-vacinação da vacinação contra a febre amarela (FA). Para este propósito, o estado de memória das células T circulantes (Naïve / efetor-precoce / Memória-Central / Memória Efetiva) e células B (Naïve / memória não clássica / memória clássica) juntamente com o perfil de citocinas (IFN / TNF / IL-5 / IL-10) foram monitorizados antes do NV (dia 0) e em pontos de tempo distintos após a vacinação primária com 17DD-YF - VP (dia30-45); PV (ano1-9) e PV (ano10-11). Um conjunto de biomarcadores (eEfCD4; EMCD4; CMCD19; EMCD8; IFNCD4; IL-5CD8; TNFCD4; IFNCD8; TNFCD8; IL-5CD19; IL-5CD4) foi observado em PV (dia30-45), mas não em NV (dia0) , com a maioria deles ainda observada em VP (ano1-9). Deficiências de biomarcadores fenotípicos / funcionais foram observadas em NV (dia 0), enquanto a falta total de atributos relacionados à memória foi observada na PV (ano10-11), independentemente da idade na vacinação primária. Análise de diagrama de Venn pré-selecionada 10 atributos (eEfCD4, EMCD4, CMCD19, EMCD8, IFNCD4, IL-5CD8, TNFCD4, IFNCD8, TNFCD8 e IL-5CD4), dos quais a média geral apresentou moderada precisão para discriminar PV (dia30-45) e PV (year1-9) de NV (day0) e PV (year10-11). Abordagens multi-parâmetro e algoritmos de árvore de decisão definiram os atributos EMCD8 e IL-5CD4 como os dois principais preditores com desempenho moderado. Juntamente com os títulos PRNT, os dois principais biomarcadores levaram a um status de memória resultante observado em 80% e 51% dos voluntários em PV (dia30-45) e PV (ano1-9), contrastando com 0% e 29% encontrados em NV ( day0) e PV (year10-11), respectivamente. A deficiência de atributos relacionados à memória observada na PV (year10-11) ressalta a diminuição conspícua dependente do tempo da memória resultante após a vacinação primária com 17DD-YF, que pode ser útil para monitorar potenciais correlatos de proteção em áreas sob risco de transmissão da FA.

Cytokines, chemokines and leukotrienes profile and signature analysis in HTLV-1 infection as an evidence of disease progression

Background: A cross-sectional study evaluated the cytokines, chemokines and leukotrienes profiles as possible biomarkers of progression to HTLV-1 associated myelopathy (HAM). Methods: Serum samples from 21 healthy blood donors (HBD), 27 asymptomatic carriers (ASC), 32 possible HAM (pHAM) and 28 HAM individuals were tested for cytokines (IL-6, IFN-γ, TNF-α, IL-2, IL-4 and IL-10), chemokines ( RANTES, MCP1, IL-8, MIG and IP-10) and leukotrienes (CysLTs and LTB-4). For each molecule tested, the HTLV-1 individuals were classified as low or high-producers taking the global median index of the HBD group as a cut off. Results: When comparing AS and pHAM individuals, AS were high-producers of IP-10 and low-producers of RANTES; pHAM were high-producers of IL-2 and low of IL-8. Besides, AS individuals presented a strong positive correlation between the regulatory cytokines IL-10 with IL-4 and between both with the pro-inflammatory cytokines IL-2 and IL-6; a negative correlation was found between RANTES and IL-2. HAM were high-producers of IL-6, IFN-γ, IP-10, LTB4, IL-4, MIG, IL-10, IL-2, presented a positive correlation of TNF-α and IFN-γ with IL-6, but this group had a positive correlation of CysLT with IL-10, IL-4 and TNF-α, contrasting with other groups. Discussion: HAM displayed a unique signature of inflammation, which was strengthened by CysLT and not counterbalanced by IL-4 and IL-10. This signature was observed in pHAM to a lower extent, becoming more evident in HAM. This profile may indicate disease progression and may serve as prognostic markers in future studies.