Associação entre as características fenotípicas e funcionais dos monócitos circulantes e a gravidade da dengue: uma revisão sistemática da literatura

Abstract

Background: Monocytes play a central role in the immunopathogenesis of dengue. They may serve as reservoirs for viral replication and directly contribute to the vascular dysfunction that characterizes severe dengue. Previous studies have demonstrated that individuals with different degrees of dengue severity exhibit distinct cytokine and chemokine profiles. Objective: To critically synthesize the available evidence regarding the association between the phenotypic and functional characteristics of circulating monocytes and dengue severity. Methods: A systematic literature search was conducted in Embase, MEDLINE via PubMed, Scopus, Web of Science, and LILACS without publication date restrictions. The search was last updated on March 3, 2026. The methodological quality of the included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. Results: Sixteen studies met the eligibility criteria and were included in the qualitative synthesis. The studies were published between 1994 and 2025 and conducted across different dengue-endemic regions. Dengue severity was predominantly classified according to the 2009 World Health Organization (WHO) guidelines, i.e., dengue without warning signs, dengue with warning signs, or severe dengue. Most studies investigated soluble mediators, whereas fewer directly assessed cellular characteristics, including circulating monocyte counts, monocyte subsets, and phenotypic surface markers. Among the soluble mediators, interleukin (IL)-1β, IL-12, IL-18, and macrophage migration inhibitory factor (MIF) were the most frequently investigated. Other biomarkers evaluated included IL-15 and soluble CD163. Only a limited number of studies directly evaluated the phenotypic or functional characteristics of circulating monocytes. Conclusions: Although IL-18 and MIF showed the most consistent association with severe dengue, current evidence regarding circulating monocyte characteristics and dengue severity remains limited and heterogeneous. Well-designed prospective studies using standardized methodologies are needed to clarify the role of monocytes in dengue immunopathogenesis and to identify reliable biomarkers of disease severity.