RESUMO
RESUMEN El dengue es una infección viral aguda transmitida por la picadura de mosquitos del género Aedes, la cual produce hasta 100 millones de infecciones anuales en el mundo. Una gran proporción de individuos infectados con el virus presentan infecciones asintomáticas. Sin embargo, de los individuos que desarrollan la enfermedad, el 95 % presentan signos y síntomas similares a una virosis común, que por lo general se autoresuelven (dengue con y sin signos de alarma). El 5 % restante puede evolucionar a manifestaciones graves, caracterizadas por hemorragias, daño orgánico, choque hipovolémico e incluso la muerte (dengue grave). Los monocitos son uno de los blancos principales de la infección producida por el virus del dengue (DENV), los cuales participan en la replicación del mismo y en la producción de una gran variedad de citoquinas que contribuyen con el daño de diferentes tejidos y órganos en respuesta a la infección. Los monocitos se dividen en tres subpoblaciones: clásica (CD14++CD16-), no clásica (CD14+CD16++) e intermedia (CD14++CD16+), las cuales poseen respuestas funcionales contrastantes en diferentes procesos inflamatorios, en cuanto a la producción de mediadores solubles e interacción con el endotelio. Los monocitos no clásicos parecen ser los principales productores de mediadores inflamatorios como el TNF-α y la IL-1β en respuesta a la infección por DENV. Por lo tanto, se propone que cada subpoblación de monocitos debe tener un papel diferencial en la inmunopatología de la enfermedad. En esta revisión se recopilan los principales aspectos de la replicación viral y la inmunopatología del dengue, así como los principales hallazgos referentes al papel de los monocitos en esta infección y además, se propone un papel potencial y diferencial de las subpoblaciones de monocitos.
SUMMARY Dengue is an acute viral infection transmitted by the bite of the mosquito belonging to the genus Aedes, which produce until 100 millions of infections worldwide per year. A high proportion of infected individuals develop an asyntomatic infection. Nevertheless, among patients that develop a clinical disease, 95 % of them show clinical signs and symptoms similar to common virosis, that in the most of the cases can recover by themselves (dengue with and without alarm signs); the remaining 5 % can evolve to severe manifestations, characterized for hemorrhages, organic damage, hypovolemic shock and death (severe dengue). Monocytes are one of the main targets of the infection by dengue virus (DENV), supporting the viral replication, contributing to the production of high levels of cytokine and the damage of different tissues and organs in response to the infection. Monocytes are divided in 3 subsets: classical (CD14++CD16-), non-classical (CD14+CD16++) and intermediate (CD14++CD16+); which have differential functional responses in the inflammatory process, regarding the production of inflammatory mediators and the interaction with the endothelium. The non-classic monocytes seem to be the main producers of inflammatory mediators such as TNF-α and IL-1β in response to DENV infection. Therefore, it is proposed that each monocyte subset may have a different role in the disease immunopathology. This review collect the main evidence regarding the viral replication and the immunopathology of dengue, also it shows the most important findings about the role of monocytes in this infection and proposes a potential differential involvement of monocytes subsets.
Assuntos
Humanos , Dengue , MonócitosRESUMO
Regulatory T cells (Tregs) inhibit the activation of the immune response which could down-regulate the systemic and focal activation observed during ischemic stroke. In fact, in animal models, Tregs infiltrate the infarcted brain and reduce the pro-inflammatory cytokine production and infarct volume, mainly in late stages of ischemia. Recently, an expansion and greater suppressive capacity of circulating Tregs after treatment with statins was observed, in addition to their cardio- and neuroprotective actions demonstrated previously. Thus, to determine whether Treg modulation mediated by statins can also be beneficial during stroke, cerebral ischemia was artificially induced in Wistar rats by transient middle cerebral artery occlusion (tMCAO) during 60 minutes with subsequent reperfusion for 7 days. Six hours after surgery, some animals were treated with atorvastatin (ATV, 10 mg/kg) or carboxymethylcellulose as vehicle at the same concentration every other day during 7 days. Some animals were sham operated as control group of surgery. Interestingly, ATV treatment prevented the development of infarct volume, reduced the neurological deficits, and the circulating and cervical lymph node CD25+FoxP3+ Treg population. Moreover, there was a reduction of glial cell activation, which correlated with decreased circulating Tregs. Remarkably, treatment with ATV induced an increase in the frequency of CD4+CD25+ T cells, in particular of those expressing CTLA-4, in brain samples. Together, these results suggest that ATV can modulate Tregs in peripheral tissue and favor their accumulation in the brain, where they can exert neuroprotective actions maybe by the reduction of glial cell activation.