Evaluation of NET role released by neutrophils in differentiation of long-lived antibody-producing cells in chronic response induced by Thalassophryne nattereri venom

Abstract

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 neutrophils as well as from CD4+ CD44+ CD40L+ Ly6C+ effector memory T cells (TeM) in inflamed tissue. Furthermore, we have provided evidence that IL-17A, as well as IL-5 produced in a context of chronic inflammatory directly influences the production of specific IgE Abs, maintenance of B1a cells and are critical for the differentiation and maintenance of ASC B220neg on inflamed peritoneal cavity. We confirmed the existence of a hierarchic process of differentiation in which Bmem CD19 positive cells differentiate depending on antigen in CD138-positive ASC secreting lgG1 Abs dependent on IL-17A. 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 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)