Eosinophils and Bacteria, the Beginning of a Story

Abstract

Eosinophils are granulocytes primarily associated with T_H2 responses to parasites or immune hyper-reactive states, such as asthma, allergies, or eosinophilic esophagitis. However, it does not make sense from an evolutionary standpoint to maintain a cell type that is only specific for parasitic infections and that otherwise is somehow harmful to the host. In recent years, there has been a shift in the perception of these cells. Eosinophils have recently been recognized as regulators of immune homeostasis and suppressors of over-reactive pro-inflammatory responses by secreting specific molecules that dampen the immune response. Their role during parasitic infections has been well investigated, and their versatility during immune responses to helminths includes antigen presentation as well as modulation of T cell responses. Although it is known that eosinophils can present antigens during viral infections, there are still many mechanistic aspects of the involvement of eosinophils during viral infections that remain to be elucidated. However, are eosinophils able to respond to bacterial infections? Recent literature indicates that Helicobacter pylori triggers T_H2 responses mediated by eosinophils; this promotes anti-inflammatory responses that might be involved in the long-term persistent infection caused by this pathogen. Apparently and on the contrary, in the respiratory tract, eosinophils promote T_H17 pro-inflammatory responses during Bordetella bronchiseptica infection, and they are, in fact, critical for early clearance of bacteria from the respiratory tract. However, eosinophils are also intertwined with microbiota, and up to now, it is not clear if microbiota regulates eosinophils or vice versa, or how this connection influences immune responses. In this review, we highlight the current knowledge of eosinophils as regulators of pro and anti-inflammatory responses in the context of both infection and naïve conditions. We propose questions and future directions that might open novel research avenues in the future.

Keywords: Th1 responses; Th2 responses; bacteria; eosinophils; homeostasis; microbiota.

Figure 1

Eosinophils promote T_H2 responses. Eosinophils responding and secreting cytokines, such as IL-4, IL-5, IL-13 and others, generates a type II immune response that can promote the generation of T_H2 responses.

Figure 2

Eosinophils promote T_H1/T_H17 responses. Eosinophils contain and secrete cytokines, such as IFNγ, TNFα, IL-17, and others, generates a type I or type III immune response against external insults, such as viral infections.

Figure 3

Eosinophilic maintenance of T_H1/T_H2 balance. Eosinophilic expression of IDO, PD-L1, and IL-1RA maintains the homeostasis between type I and type II immune responses. Generally, the secretion of these molecules is to control over-reactive pro-inflammatory responses.

Figure 4

Cross-signaling between eosinophils and microbiota. (A) Summary of some processes in which murine microbiota is involved. (B) Alterations observed in eosinophil-deficient mice. (C) Alterations observed in germ-free (GF) mice.