Eosinophils release DNA extracellular traps in response to Candida albicans hyphae

Eosinophils are granulocytes associated with allergic inflammatory diseases, such as rhinosinusitis, asthma, and allergic bronchopulmonary mycoses (ABPMs). ABPMs are hypersensitivity conditions caused by repeated exposure of asthmatic individuals to filamentous fungi, being Aspergillus fumigatus the most common cause. Despite fungi being a common source of allergens, how eosinophils recognize and respond to these microorganisms is poorly understood. The release of DNA extracellular traps is one of the mechanisms leukocytes deploy against fungi, and several species are known to induce the release of these structures by neutrophils. In previous works, our group showed that A. fumigatus induce the release of eosinophil extracellular traps (EETs)¹, but it is still unknown whether this mechanism is conserved in the eosinophilic response against filamentous fungi. Candida albicans is a dimorphic fungus found as a commensal in human mucosas that can cause diseases ranging from superficial infections to life-threatening candidemia. C. albicans is also the second most common cause of ABPMs. Therefore, in the present work we used fluorometric assays and confocal microscopy to assess the release of EETs by human eosinophils isolated from healthy donors (institutional review board approved protocol: CAAE 31968020.9.0000.5257) and stimulated in vitro with C. albicans yeasts and hyphae, as well as with a yeast-locked strain of C. albicans. We found that hyphae-stimulated eosinophils release greater levels of EETs than those stimulated with yeasts, and that opsonization increase EETs release against yeasts. When stimulated with the yeast-locked strain, EET release was severely lower, which suggests that EET release is an eosinophilic response specific to filamentous morphotype. These results contribute to the understanding of eosinophilic response against fungi, and points to EETs as a possible mechanism involved in ABPM pathogenesis.

¹J Allergy Clin Immunol (2018) 141:571