Impact of efferocytosis of ZIKV-infected cells on the activation of dendritic cells and on the differentiation of autoreactive T lymphocyte clones

• Grant number: 21/02506-5
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2021 - October 31, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandra Ivo de Medeiros
• Grantee: Alexandra Ivo de Medeiros
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Ana Paula Moreira Serezani ; Carlos Henrique Cardoso Serezani ; Naiara Naiana Dejani

Abstract

The development of some autoimmune diseases has been associated with genetic pre-dispositions and the phenomenon of molecular mimicry initiated by pathogens due to previous infections. However, recent studies have shown that phagocytosis, by dendritic cells (DCs), of infected-apoptotic cells, a process called efferocytosis, can result in the activation of autoreactive T-cells clones. In this context, the efferocytosis of infected-apoptotic cells with Citrobacter rodentium results in the presentation of self MHC antigens and antigens of the microbe, promoting an environment conducive to the activation of clones of autoreactive Th17 lymphocytes. Infection with the Zika virus (ZIKV) has gained attention from the scientific community due to a large number of cases of microcephaly and neurological complications, such as Guillain-Barré syndrome (GBS) and acute disseminated encephalomyelitis (ADEM). Other studies have shown that the infection by ZIKV induce apoptosis in neural progenitor cells. In humans, the detection of ZIKV and inflammatory cytokines in the cerebrospinal fluid of individuals with severe neurological disorders has been described. However, it is still unknow the correlation between efferocytosis of ZIKV-infected cells and DC maturation, as well as the production of inflammatory cytokines and self-reactive CD4+ T lymphocyte trigging autoimmune diseases. Considering that ZIKV infections induce intense death by apoptosis of different cell types, such as neural progenitor cells and immature neurons, we hypothesized that during the ZIKV-infectious, the efferocytosis of infected-apoptotic cells could induce activation and maturation of DCs that allow the expression of both self-and ZIKV-peptides by MHC class II molecules and lead to the activation of autoreactive CD4+ T lymphocyte clones. (AU)