Type 1 Innate Lymphoid Cell and Natural Killer Cells Are Sources of Interferon-γ and Other Inflammatory Cytokines Associated With Distinct Clinical Presentation in Early Dengue Infection

• Published in: The Journal of infectious diseases 2022-01, Vol.225 (1), p.84-93
• Main Authors: Quintino-de-Carvalho, Iracema Luisa, Gonçalves-Pereira, Marcela Helena, Faria Ramos, Michele, de Aguiar Milhim, Bruno Henrique Gonçalves, Da Costa, Último Libânio, Santos, Érika Gonçalves, Nogueira, Maurício Lacerda, Da Costa Santiago, Helton
• Format: Article
• Language: English
• Subjects: CD56 antigen; Cytokines; Cytokines - immunology; Cytokines - metabolism; Dengue hemorrhagic fever; Fever; Flow cytometry; Humans; Immunity, Innate; Infections; Inflammation; Interferon-gamma; Interleukin 13; Interleukin 17; Killer Cells, Natural - immunology; Leukocytes, Mononuclear; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Lymphocytes; Lymphoid cells; Natural killer cells; Peripheral blood mononuclear cells; Severe Dengue - blood; Severe Dengue - immunology; γ-Interferon
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiab312

Abstract Background Increased levels of inflammatory cytokines are associated with severe dengue evolution, but the source of such hypercytokinemia is elusive. We investigated the contribution of innate lymphocytes, innate lymphoid cells (ILCs), and natural killer (NK) cells in cytokine production in early dengue infection. Methods Peripheral blood mononuclear cells of individuals with dengue without warning signs (DWS–) and dengue with warning signs and severe dengue (SD) presentation combined (DWS+) were obtained between 2 and 7 days since fever onset and submitted to flow cytometry without specific antigen stimulation to evaluate cytokines in ILC and NK cell subpopulations. Results ILCs and NK cells were found to be important sources of cytokines during dengue. ILCs of the DWS+/SD group displayed higher production of interferon gamma (IFN-γ) and interleukin (IL) 4/IL-13 when compared to DWS– individuals. On the other hand, NK Eomes+ cells of DWS– patients displayed higher IFN-γ production levels compared with the DWS+/SD group. Interestingly, when NK cells were identified by CD56 expression, DWS+/SD displayed higher frequency of IL-17 production compared with the DWS– group. Conclusions These results indicate that ILCs and NK cells are important sources of inflammatory cytokines during acute dengue infection and display distinct profiles associated with different clinical forms.