Exosomes released from macrophages infected with Talaromyces marneffei activate the innate immune responses and decrease the replication.

Abstract

Recent studies have demonstrated that exosomes play roles in pathogenesis and in the treatment of various diseases. We explored the influence of exosomes released from Talaromyces marneffei (T. marneffei)-infected macrophages on human macrophages to determine whether they play a role in the pathogenesis of T. marneffei infection. Exosomes derived from macrophages infected with T. marneffei were extracted and characterized by transmission electron microscopy and western blot. Moreover, we examined exosomes that modulated IL-10 and TNF-α secretion and activation of p42 and p44 extracellular signal-regulated kinase 1 and 2 (ERK1/2) and activation of autophagy. We found that exosomes promoted activation of ERK1/2 and autophagy, IL-10 and TNF-α secretion in human macrophages. Further, exosomes decreased the multiplication of T. marneffei in T. marneffei-infected human macrophages. Interestingly, exosomes isolated from T. marneffei-infected but not from uninfected macrophages can stimulate innate immune responses in resting macrophages. Our studies are the first to demonstrate that exosomes isolated from T. marneffei-infected macrophages can modulate the immune system to control inflammation, and we hypothesize that exosomes play significant roles in activation of ERK1/2 and autophagy, the replication of T. marneffei and cytokine production during T. marneffei infection.