T-cells producing multiple combinations of IFN gamma, TNF and IL10 are associated with mild forms of dengue infection
IMMUNOLOGY
Authors: Goncalves Pereira, Marcela Helena; Figueiredo, Maria Marta; Queiroz, Camila Pereira; Barros Magalhaes, Telcia Vasconcelos; Mafra, Adriana; Oliveira Diniz, Lilian Martins; da Costa, Ultimo Libanio; Gollob, Kenneth J.; do Valle Antonelli, Lis Ribeiro; Santiago, Helton da Costa
Abstract
Multifunctional interleukin 10 (IL10)(+)Th1 cells have been implicated in favorable evolution of many infectious diseases, promoting an efficacious immune response while limiting immunopathology. Here, we investigated the presence of multifunctional CD4(+) and CD8(+) T-cells that expressed interferon gamma (IFN gamma), IL10 and tumor necrosis factor (TNF), or its combinations during dengue infection. Peripheral blood mononuclear cells (PBMCs) from outpatients with dengue (mild dengue forms) and hospitalized patients (or patients with dengue with warning signs and severe dengue) were cultured in the presence of envelope (ENV) or NS3 peptide libraries of DENV during critical (hospitalization period) and convalescence phases. The production of IFN gamma, IL10 and TNF by CD4(+) and CD8(+) T-cells was assessed by flow cytometry. Our data show that patients with mild dengue, when compared with patients with dengue with warning signs and severe dengue, presented higher frequencies of multifunctional T-cells like NS3-specific IFN gamma/IL10-producing CD4(+) T-cells in critical phase and NS3- and ENV-specific CD8(+) T-cells producing IFN gamma/IL10. In addition, NS3-specific CD8(+) T-cells producing high levels of IFN gamma/TNF and IFN gamma/TNF/IL10 were also observed in the mild dengue group. We observed that multifunctional T-cells produced higher levels of cytokines as measured by intracellular content when compared with single producer T-cells. Importantly, multifunctional CD4(+) and CD8(+) T-cells producing IFN gamma, TNF and IL10 simultaneously displayed positive correlation with platelet levels, suggesting a protective role of this population. The presence of IL10(+)Th1 and IL10(+)Tc1 multifunctional cells was associated with mild dengue presentation, suggesting that these cells play a role in clinical evolution of dengue infection.
Trichinella spiralis muscle larvae release extracellular vesicles with immunomodulatory properties
PARASITE IMMUNOLOGY
Authors: Kosanovic, Maja; Cvetkovic, Jelena; Gruden-Movsesijan, Alisa; Vasilev, Sasa; Svetlana, Milanovic; Ilic, Natasa; Sofronic-Milosavljevic, Ljiljana
Abstract
Aims Extracellular vesicles (EVs) represent a newly discovered but universal communication tool between cells or organisms. However, few data exist on nematode EVs and none for Trichinella spiralis. Here, we aimed to investigate whether T spiralis muscle larvae produce EVs, whether they carry immunomodulatory proteins and whether they have a role in immunomodulation as a component of excretory-secretory muscle larvae products (ES L1). Methods and results EVs were enriched from conditioned medium of T spiralis muscle larvae. Transmission electron microscopy images showed T spiralis EVs to be 30-80 nm in size, and Western blot confirmed the presence of two out of three glycoproteins with the immunodominant epitope characteristic for muscle larvae of the genus Trichinella. Using a peripheral blood mononuclear cell (PBMC) stimulation assay, it was shown that these EVs elevated production of IL10 and IL6. Conclusion T spiralis muscle larvae produce EVs. Those EVs carry immunomodulatory proteins and have the capacity independently to induce regulatory responses in the same way as the T spiralis excretory-secretory muscle larvae products from which they were isolated.