Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity

Coakley G, McCaskill JL, Borger JG, Simbari F, Robertson E, Millar M, Harcus Y,

McSorley HJ, Maizels RM, Buck AH.

Cell Rep. 2017 May 23; 19(8):1545-1557

Speaker: Chia-Yun Tsai (蔡佳芸)                             Time: 15:00~16:00, Sep. 27, 2017

Commentator: Dr. Jyh-Wei Shin (辛致煒老師)       Place: Room 601

Abstract:

Extracellular vesicles (EVs) released by a wide spectrum of parasites have been described as a newly recognized vehicles in cross-species communication [1]. Recent reports demonstrated that EVs provide a mechanism for shuttling parasite cargo into host cells, including virulence factors from diverse pathogens [2]. However, the mode of specific interaction between EVs and immune cells during infection remain to be elucidated. In this study, the authors found that macrophages efficiently take up EVs derived from gastrointestinal nematode Heligmosomoides polygyrus, leading to diminished levels of type 1 and type 2 effector molecules, such as IL-6 and TNF or Ym1 and RELMα. These results indicated the suppression of both classical and alternative activation in macrophages. Independently, internalization of EVs inhibited ST2/IL-33R signaling pathway which can be functionally blocked by the addition of EV-specific antibodies. Moreover, targeting EVs by vaccination stimulated strong antibody responses and engendered protective immunity against infection in vivo, while worm expulsion failed in ST2-deficient mice. In summary, the authors illustrated the ability of helminth-derived EVs to modulate the onset of alternative activation and IL-33 signaling pathway, strengthening them as crucial virulence factors. Besides, vaccination against EVs generated specific antibodies and was sufficient to interrupt infection by H.polygyrus. These findings have revealed a better understanding of the properties of a role for EVs in parasite-host crosstalk.

References:

1.         Coakley, G., R.M. Maizels, and A.H. Buck, "Exosomes and Other Extracellular Vesicles: The New Communicators in Parasite Infections." Trends Parasitol, 2015. 31(10): p. 477-89.

2.         Buck, A.H., et al., "Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity." Nat Commun, 2014. 5: p.5488.