Mouse Eosinophils Possess Potent Antibacterial Properties In Vivo

Abstract

Eosinophils are best known as the predominant cellular infiltrate associated with asthma and parasitic infections. Recently, numerous studies have documented the presence of Toll-like receptors (TLRs) on the surfaces of eosinophils, suggesting that these leukocytes may participate in the recognition and killing of viruses and bacteria. However, the significance of this role in the innate immune response to bacterial infection is largely unknown. Here we report a novel role for eosinophils as antibacterial defenders in the host response. Isolated mouse eosinophils possessed antipseudomonal properties in vitro. In vivo, interleukin-5 transgenic mice, which have profound eosinophilia, demonstrated improved clearance of Pseudomonas aeruginosa introduced into the peritoneal cavity. The findings of improved bacterial clearance following adoptive transfer of eosinophils, and impaired bacterial clearance in mice with a congenital eosinophil deficiency, established that this effect was eosinophil specific. The data presented also demonstrate that eosinophils mediate this antibacterial effect in part through the release of cationic secondary granule proteins. Specifically, isolated eosinophil granules had antibacterial properties in vitro, and administration of eosinophil granule extracts significantly improved bacterial clearance in vivo. These data suggest a potent yet underappreciated antibacterial role for eosinophils in vivo, specifically for eosinophil granules. Moreover, the data suggest that the administration of eosinophil-derived products may represent a viable adjuvant therapy for septic or bacteremic patients in the intensive care unit.

Eosinophils Contribute to IL-4 Production and Shape the T-Helper Cytokine Profile and Inflammatory Response in Pulmonary Cryptococcosis

“…69 Eosinophils demonstrate protective mechanisms that rely on degranulation in bacterial infections 70 and release mitochondrial DNA in a unique way that clumps bacteria together. 71 In addition, antiviral effects have been reported.…”

The expanding role(s) of eosinophils in health and disease

“…We would suggest that the remarkably complex immunity of the gut occurring as a consequence of the bacterial burden of this compartment (and the necessary containment it requires of the host) may explain why uniquely the gastrointestinal tract has a rather robust resident eosinophil population. Interestingly, although the primary function of these eosinophils may be immunoregulative in character, recent observations of unique antibacterial activities 97,98 may be equally underappreciated effector functions of these gut-associated granulocytes.…”

Interleukin 5 Is Protective during Sepsis in an Eosinophil-Independent Manner

“…This was believed to be caused by the antibacterial properties of eosinophils, because we have previously demonstrated that eosinophil-deficient (PHIL) mice have increased susceptibility to bacterial sepsis (22,34). To establish whether eosinophils were necessary for the protective effects of IL-5 in sepsis, NJ.1638 mice were crossed with PHIL 1/2 mice, which express a diphtheria toxin transgene under control of the eosinophil peroxidase promoter (28,29).…”

“…Growing data suggest eosinophils play a protective role in the innate immune response to sepsis (21,22). Interleukin 5 (IL-5) is the primary hematopoietic cytokine responsible for eosinophil growth and maturation.…”