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Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non‐classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non‐classical monocytes in patients compared with controls. With this finding, we focused on studying the phenotype of non‐classical monocytes in the present study. An increase in activation and differentiation markers, such as CD64, CD86, the percentage of tumor necrosis factor‐α (+) cells and exposure of phosphatidylserine, were recorded in the non‐classical monocytes of patients compared with controls. Moreover, a significant decrease in the expression of CX3CR1 with a corresponding increase in the expressions of CCR2, CCR5, CD11b and CD54 was detected in the non‐classical monocytes of patients in comparison with that of the controls. Significant increases in the frequency of microparticles from endothelium and in the concentrations of interleukin‐6 (IL‐6), IL‐8 and IL‐10 were noted in the plasma of patients. These findings demonstrate that in patients with dengue, non‐classical monocytes are activated, exhibiting a phenotype associated with more differentiation, produces tumor necrosis factor‐α and has a profile of less endothelial surveillance closer to the cellular migration. These changes were associated with hepatic compromise, endothelial alteration and high concentration of circulating cytokines. Hence, alterations of non‐classical monocytes seem to be associated with the immunopathology of dengue infection.

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.