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Evaluation the mechanisms involved in the survival of long-lived antibody-secreting cells induced by IL-17- released from neutrophil extracellular traps

Grant number: 15/12225-2
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): September 01, 2015
Effective date (End): November 30, 2015
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Carla Lima da Silva
Grantee:Lidiane Zito Grund
Supervisor: Bernhard Ryffel
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Research place: Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), France  
Associated to the scholarship:13/50694-9 - Evaluation of NET role released by neutrophils in differentiation of long-lived antibody-producing cells in chronic response induced by Thalassophryne nattereri venom, BP.PD


Recently we demonstrated that Thalassophryne nattereri (Niquim) fish venom induces the formation of a protective immune response characterized by memory B cells (Bmem) and the long-lived antibody-secreting cells (ASC). From a combined in vivo and in vitro approaches we have demonstrated that the generation of ASC (B220neg) on BALB/c mice is related to the production of survival factors from mast cells, eosinophils and mainly neutrophils, as well as from effector memory T cells (CD4+CD44+CD40L+Ly6C+, TeM) in inflamed tissue. Furthermore, we have provided evidence that both IL-17A and IL-5 produced in a chronic inflamed peritoneal cavity directly influence the production of specific IgE Abs, the maintenance of B1a cells and are critical for the differentiation and maintenance of ASC B220neg. We confirmed the existence of a hierarchic process of differentiation in which CD19-positive Bmem differentiate in CD138-positive ASC secreting IgG1 Abs dependent on IL-17A and antigen. Given the chronic recruitment of neutrophils induced by venom, the role of IL-17A in the differentiation of functional ASC and recent researches showing the important immunomodulatory actions of NET (neutrophil extracellular traps) on the innate and adaptive immune system as a cellular source of IL-17A, in this work we sought to explore the role of NET released by neutrophils as source of ideal stimuli, especially IL-17A, for the generation and survival of ASC. The elucidation of role of NET and their implications on maintaining immunological memory in physiological or pathological conditions can be the basis for understanding the protective memory maintenance to different antigens and could be the initial step for development of new alternatives for vaccination. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DOS SANTOS, JANAINA CARDOSO; GRUND, LIDIANE ZITO; SEIBERT, CARLA SIMONE; MARQUES, ELINEIDE EUGENIO; SOARES, ANDERSON BRITO; QUESNIAUX, VALERIE F.; RYFFEL, BERNHARD; LOPES-FERREIRA, MONICA; LIMA, CARLA. Stingray venom activates IL-33 producing cardiomyocytes, but not mast cell, to promote acute neutrophil-mediated injury. SCIENTIFIC REPORTS, v. 7, . (13/07467-1, 15/12224-6, 15/12225-2)
GRUND, LIDIANE ZITO; NOVASKI, IVAN; QUESNIAUX, VALERIE F.; RYFFEL, BERNHARD; LOPES-FERREIRA, MONICA; LIMA, CARLA. Neutrophils releasing IL-17A into NETs are essential to plasma cell differentiation in inflamed tissue dependent on IL-1R. AUTOIMMUNITY, v. 50, n. 2, p. 86-101, . (15/12225-2, 13/50694-9)

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