4.7 Article

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

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 225, Issue 1, Pages 84-93

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab312

Keywords

dengue; innate lymphocytes; ILC1; NK cells; IFN-gamma; cytokine storm; inflammation

Funding

  1. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [404138/2012-8]
  2. Fundacao de Amparo a Pesquisa de Minas Gerais [APQ-03452-13]
  3. Fundacao de Apoio a Pesquisa do Estado de Sao Paulo [13/21719-3]
  4. Instituto Nacional de Ciencia e Tecnologia em Vacinas (INCT-V)
  5. Program for Technological Development in Tools for Health (PDTISFIOCRUZ, Flow Cytometry Platform)
  6. Flow Cytometry core facility of the Pharmacy School of Universidade Federal de Minas Gerais

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ILCs and NK cells are important sources of inflammatory cytokines during acute dengue infection, with distinct profiles associated with different clinical forms.
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-gamma) and interleukin (IL) 4/IL-13 when compared to DWS- individuals. On the other hand, NK Eomes(+) cells of DWS- patients displayed higher IFN-gamma 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. Mese 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.

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