Differential regulation of Type 1 and Type 2 mouse eosinophil activation by apoptotic cells

Abstract

Eosinophils are multifunctional, evolutionary conserved leukocytes that are involved in a plethora of responses ranging from regulation of tissue homeostasis, host defense and cancer. Although eosinophils have been studied mostly in the context of Type 2 inflammatory responses, it is now evident that they participate in Type 1 inflammatory responses and can respond to Type 1 cytokines such as IFN-γ. Notably, both Type 1- and Type 2 inflammatory environments are characterized by tissue damage and cell death. Collectively, this raises the possibility that eosinophils can interact with apoptotic cells, which can alter eosinophil activation in the inflammatory milieu. Herein, we demonstrate that eosinophils can bind and engulf apoptotic cells. We further show that exposure of eosinophils to apoptotic cells induces marked transcriptional changes in eosinophils, which polarize eosinophils towards an anti-inflammatory phenotype that is associated with wound healing and cell migration. Using an unbiased RNA sequencing approach, we demonstrate that apoptotic cells suppress the inflammatory responses of eosinophils that were activated with IFN-γ + E. coli (e.g., Type 1 eosinophils) and augment IL-4-induced eosinophil activation (e.g., Type 2 eosinophils). These data contribute to the growing understanding regarding the heterogeneity of eosinophil activation patterns and highlight apoptotic cells as potential regulators of eosinophil polarization.

The neurotropic schistosome vs experimental autoimmune encephalomyelitis: are there any winners?

“…However, the nervous tissue was also infiltrated by many eosinophils which polarize to 'type 1' cells when stimulated by IFN-γ (Dolitzky et al, 2021(Dolitzky et al, , 2022. These cells have markers similar to those of M1 macrophages, such as Cd86, Cd53 and Cd36 (Dolitzky et al, 2021).…”

“…These cells have markers similar to those of M1 macrophages, such as Cd86 , Cd53 and Cd36 (Dolitzky et al ., 2021 ). Type 1 eosinophils can produce other inflammatory cytokines (Sakkal et al ., 2016 ; Dolitzky et al ., 2021 ), and their ability to repair the tissue and stimulate M2 polarization is allayed (Dolitzky et al ., 2021 , 2022 ). Furthermore, eosinophils can forge even more IFN- γ (Lucarini et al ., 2017 ) and create a stimulatory loop and inflammatory milieu.…”

Ally, adversary, or arbitrator? The context-dependent role of eosinophils in vaccination for respiratory viruses and subsequent breakthrough infections

“…Eosinophils, particularly those that have been stimulated with type 1–skewing agents such as lipopolysaccharide and IFN-γ, can upregulate surface expression of PD-L1. 151 , 210 , 211 PD-L1 binding to PD-1 on T cells counterbalances activation, allowing for a balance between cytotoxic destruction of infected cells and maintenance of tissue integrity. 212 PD-L1 can bind to costimulatory, activating molecule CD80 on immune cells in an inhibitory manner as well.…”

Eosinophils in the tumor microenvironment: implications for cancer immunotherapy

“…A recent study showed the plasticity of eosinophils where eosinophils experienced transcriptional changes toward anti-inflammatory functions such as wound healing and cell migration upon interacting with apoptotic cells. Apoptotic cells suppress IFN-γ-mediated eosinophil activation and polarize them toward IL-4-induced type 2 responses including tissue repair and remodeling [ 56 ]. The following outlines discuss how eosinophils impact TME components (Fig.…”