Exosomes released from macrophages infected with Talaromyces marneffei
activate the innate immune responses and reduce intracellular
multiplication
Abstract
Recent studies have shown that exosomes are involved in pathogenesis and
in the treatment of various tumors and inflammatory diseases. We
examined the impacts 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 were extracted using commercial kits
and characterized by transmission electron microscopy and western blot.
Further, we examine exosomes that regulate IL-10 and TNF-α production
and activation of p42 and p44 extracellular signal-regulated kinase 1
and 2 (ERK1/2) and activation of autophagy. We found that exosomes
induced activation of ERK1/2 and autophagy, IL-10 and TNF-α production
in human macrophages. Furthermore, exosomes decreased the replication of
T. marneffei in T. marneffei-infected human macrophages. Interestingly,
exosomes isolated from T. marneffei-infected but not from uninfected
macrophages can stimulate a proinflammtory response in resting
macrophages. Our studies are the first to demonstrate that exosomes
isolated from T. marneffei-infected macrophages can induce a
proinflammatory response, and we hypothesize that exosomes play
significant roles in activation of ERK1/2 and autophagy, the replication
of T. marneffei and cytokine release during T. marneffei infection.