AbstractIntroductionRecent studies have demonstrated that exosomes play roles in pathogenesis and in the treatment of various diseases. We explored the influence of exosomes released fromTalaromyces marneffei(T. marneffei)‐infected macrophages on human macrophages to determine whether they play a role in the pathogenesis ofT. marneffeiinfection.MethodsExosomes derived from macrophages infected withT. marneffeiwere 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.ResultsWe found that exosomes promoted activation of ERK1/2 and autophagy, IL‐10 and TNF‐α secretion in human macrophages. Further, exosomes decreased the multiplication ofT. marneffeiinT. marneffei‐infected human macrophages. Interestingly, exosomes isolated fromT. marneffei‐infected but not from uninfected macrophages can stimulate innate immune responses in resting macrophages.ConclusionOur studies are the first to demonstrate that exosomes isolated fromT. 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 ofT. marneffeiand cytokine production duringT. marneffeiinfection.