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.

Ébolavirus: biología molecular y evasión de la respuesta inmune / Ebolavirus: molecular biology and immune response evasion

La actual epidemia de enfermedad por virus Ébola que azota al África Occidental ha cobrado la vida de alrededor de 9 000 personas con más de 22 000 infectados en seis países, y algunos casos aislados han llegado a ciudades de Europa y Estados Unidos. Aunque el curso clínico de la enfermedad es bien conocido, los mecanismos específicos que explican su patogenicidad no han sido completamente delineados. Los casos fatales de infección por Ébolavirus están marcados por un fallo catastrófico de las respuestas inmune innata y adaptativa, mediado por proteínas codificadas por el virus, así como por propiedades asociadas a su estructura. El genoma del Ébolavirus está constituido solamente por siete genes que codifican unas 10 proteínas, suficientes para desencadenar una enfermedad cuya letalidad varía del 40 al 90 por ciento. En el centro de la desregulación inducida por el Ébola se encuentra una temprana y coordinada actuación de las proteínas VP24, VP30 y VP35, que conduce a niveles elevados de replicación viral, a una inapropiada temporización de la cascada de liberación de linfocinas y a la muerte, tanto de células presentadoras de antígenos, como de células efectoras. Los complejos mecanismos del Ébola para regular selectivamente la respuesta inmune y su patogenicidad variable en diferentes especies hospederas, convierten a este virus en un adversario formidable, así como de un notable interés científico(AU)

The current Ebolavirus disease outbreak that strikes West Africa has claimed the life of around 9 000 people and has infected more than 22 000 in six countries, and some isolated cases have reached cities of Europe and the United States. Though the clinical course of the disease is well known, the specific mechanisms of its pathogenicity have not been fully delineated yet. Fatal cases of Ebolavirus disease are marked by a catastrophic failure of both innate and adaptive immune responses, mediated by virus-encoded proteins as well as properties associated with its structure. Ebolavirus genome comprises only seven genes encoding about 10 proteins, enough to cause a disease which fatality fluctuates from 40 to 90 percent. At the heart of Ebola-induced immune dysregulation is an early and coordinated disruption by VP24, VP30, and VP35 that leads to elevated levels of virus replication, a cascade of inappropriately timed cytokine release, and death of both antigen-presenting and responding immune cells. The complex mechanisms of Ebola to selectively regulate immune responses and its variable pathogenicity in different host species makes this virus both, a challenging foe and scientifically interesting(AU)

Evasion of immune responses by Trypanosoma cruzi, the etiological agent of Chagas disease

Infection with the protozoan parasite Trypanosoma cruzi leads to Chagas disease, which affects millions of people in Latin America. Infection with T. cruzi cannot be eliminated by the immune system. A better understanding of immune evasion mechanisms is required in order to develop more effective vaccines. During the acute phase, parasites replicate extensively and release immunomodulatory molecules that delay parasite-specific responses mediated by T cells. This immune evasion allows the parasite to spread in the host. In the chronic phase, parasite evasion relies on its replication strategy of hijacking the TGF-β signaling pathway involved in inflammation and tissue regeneration. In this article, the mechanisms of immune evasion described for T. cruzi are reviewed.