Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation

Abstract

Eosinophils are predominantly known for their contribution to allergy. Here, we have examined the function and regulation of gastrointestinal eosinophils in the steady-state and during infection with or We find that eosinophils are recruited to sites of infection, directly encounter live bacteria, and activate a signature transcriptional program; this applies also to human gastrointestinal eosinophils in humanized mice. The genetic or anti-IL-5-mediated depletion of eosinophils results in improved control of the infection, increased inflammation, and more pronounced Th1 responses. Eosinophils control Th1 responses via the IFN-γ-dependent up-regulation of PD-L1. Furthermore, we find that the conditional loss of IFN-γR in eosinophils phenocopies the effects of eosinophil depletion. Eosinophils further possess bactericidal properties that require their degranulation and the deployment of extracellular traps. Our results highlight two novel functions of this elusive cell type and link it to gastrointestinal homeostasis and anti-bacterial defense.

Deciphering the role of eosinophils in solid organ transplantation

“…Eosinophils modulate immunity against various infectious pathogens. These include infection with helminth, nematode microfilariae, viral infection, and infection with bacteria . The protective impact of eosinophils against infectious agents varies depending on the stage of infection and the type of infectious agent to include either killing of the agent or limitation of growth/symbiotic relationship.…”

“…The protective impact of eosinophils against infectious agents varies depending on the stage of infection and the type of infectious agent to include either killing of the agent or limitation of growth/symbiotic relationship. For example, eosinophil exposure to Clostridium rodentium induced killing through formation of eosinophil extracellular DNA traps and yet eosinophil exposure to Helicobacter pylori triggered immune mechanisms that permitted bacterial survival in the host . In general, direct killing mechanisms include release of granule proteins, enzymes, and release of DNA extracellular traps .…”

Impact of eosinophil-peroxidase (EPX) deficiency on eosinophil structure and function in mouse airways

“…The role of PRRs in modulating eosinophil-mediated interactions with bacteria, including phagocytosis and generation of extracellular traps is likewise a subject that remains to be explored [6, 10]. …”

“…As noted above and in the paragraph to follow, until relatively recently [6, 9, 10, 56, 66], eosinophils were not perceived as having specific, physiologically meaningful interactions with bacteria.…”

“…In the absence of disease, eosinophils are prominent in the small intestines, where they are poised to interact directly with macrophages, dendritic cells, B and T lymphocytes, and to direct mucosal immunity at this interface [5, 6]. While eosinophils are required for full support of IgA-producing plasma cells in the gastrointestinal tract and have been implicated in promoting microbiome homeostasis and protection against gastrointestinal infection [7–10], eosinophil-deficient mice are not overly handicapped in the absence of extreme provocation [11]. An improved understanding of eosinophils is clearly needed, including their homeostatic as well as their dysregulated responses.…”