Research Papers: Immunology:

Endotoxin tolerance modulates TREG and TH17 lymphocytes protecting septic mice

Mariana M.C. Andrade, Suely S.K. Ariga, Denise F. Barbeiro, Hermes V. Barbeiro, Rosangela N. Pimentel, Ricardo C. Petroni and Francisco G. Soriano _

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Oncotarget. 2019; 10:3451-3461. https://doi.org/10.18632/oncotarget.26919

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Mariana M.C. Andrade1, Suely S.K. Ariga1, Denise F. Barbeiro1, Hermes V. Barbeiro1, Rosangela N. Pimentel1, Ricardo C. Petroni1 and Francisco G. Soriano1

1Laboratório de Investigação Médica – LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil

Correspondence to:

Francisco G. Soriano, email: [email protected]

Keywords: sepsis; lymphocytes; Treg; Th17; tolerance

Received: May 05, 2018    Accepted: March 23, 2019    Published: May 28, 2019


Background: Tolerance induces a regulated immune response to infection. We hypothesized that tolerance induction modulated profile of T regulatory cell (Treg) and T lymphocyte 17 (Th17) cells and is related cytokine released in septic animals. Methods: Male black C57/6 mice received subcutaneous (s.c.) injections of lipopolysaccharide (LPS) (1 mg/kg) for 5 days, on day 8th was made cecal ligation and puncture (CLP). Blood and spleen tissue were collected for cell analysis and cytokines measurements. Results: Cytokines (interleukin 2 (IL-2), interleukin (IL-6), transforming growth factor β (TGF-β) and interferon γ (INF-γ)) related to Treg and Th17 stimulation were elevated in the spleen of tolerant animals compared to sham. Treg and Th17 lymphocytes showed an increased amount in blood (Treg: 920 ± 84 cells vs. 1946 ± 65 cells, sham vs. tolerant; Th17:38321± 1954 cells vs. 43526 ± 7623 cells, sham vs. tolerant) and spleen (Treg: 5947 ± 273 cells vs. 16521 ± 486 cells, sham vs. tolerant; Th17: 26543 ± 2944 cells vs. 64567 ± 5523 cells, sham vs. tolerant). Treg (135±23 cells) and Th17 (1590 ± 256 cells) cells were reduced in blood of septic animals compared to sham, while CLP tolerant animals presented an increasing number of these cells. Lymphocyte Th17IL6+ were elevated in tolerant and CLP tolerant animals in the blood compared to sham. Conclusion: LPS tolerance was associated with increasing population of Treg and Th17. LPS tolerance reduces the hyper inflammatory response with immunoregulation exerted by Treg and Th17 cells protecting from septic damage.

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