Can extracellular vesicles produced during infection by Trypanosoma cruzi function as damage-associated molecular patterns in the host?

Abstract Blood pathogenic trypanosomatids as Trypanosoma cruzi, the causative agent of Chagas Disease, have specialized systems to export virulence factors into host cells. Extracellular vesicles shed by T. cruzi promote infection susceptibility of host cells. Sterile inflammation is part of the innate immune response to molecules released upon tissue injury and is collectively indicated as damage-associated molecular patterns. The complex regulatory pathways that modulate the generation and trafficking of damage-associated molecular patterns are being actively investigated, given their potential to provide a relevant understanding of the physiological and pathological conditions of various diseases that affect humans. However, the common biochemical pathway in the generation of damage-associated molecular patterns and extracellular vesicles shed by T. cruzi is unclear. I propose the following hypothesis: some contents of extracellular vesicles from T. cruzi-infected cells can act as damage-associated molecular patterns during T. cruzi infection. This hypothesis is based on two elements to support it: first, damage-associated molecular patterns can be secreted or exposed by living cells undergoing a life-threatening stress. The second is the composition of extracellular vesicles shed by T. cruzi and released by the host cells during T. cruzi infection. Additionally, we discuss the implications of extracellular vesicles shed by T. cruzi and damage-associated molecular patterns in Chagas disease.