Leishmania mexicana: Novel Insights of Immune Modulation through Amastigote Exosomes
Por:
Enedina Soto-Serna, Laura, Diupotex, Mariana, Zamora-Chimal, Jaime, Ruiz-Remigio, Adriana, Delgado-Dominguez, Jose, Cervantes-Sarabia, Rocely Buenaventura, Mendez-Bernal, Adriana, Reyna Escalona-Montano, Alma, Magdalena Aguirre-Garcia, Maria, Becker, Ingeborg
Publicada:
3 dic 2020
Resumen:
Exosomes are extracellular microvesicles of endosomal origin
(multivesicular bodies, MVBs) constitutively released by eukaryotic
cells by fusion of MVBs to the plasma membrane. The exosomes from
Leishmania parasites contain an array of parasite molecules such as
virulence factors and survival messengers, capable of modulating the
host immune response and thereby favoring the infection of the host. We
here show that exosomes of L. mexicana amastigotes (aExo) contain the
virulence proteins gp63 and PP2C. The incubation of aExo with bone
marrow-derived macrophages (BMMs) infected with L. mexicana led to their
internalization and were found to colocalize with the cellular
tetraspanin CD63. Furthermore, aExo inhibited nitric oxide production of
infected BMMs, permitting enhanced intracellular parasite survival.
Expressions of antigen-presenting (major histocompatibility complex
class I, MHC-I, and CD1d) and costimulatory (CD86 and PD-L1) molecules
were modulated in a dose-dependent fashion. Whereas MHC-I, CD86 and
PD-L1 expressions were diminished by exosomes, CD1d was enhanced. We
conclude that aExo of L. mexicana are capable of decreasing microbicidal
mechanisms of infected macrophages by inhibiting nitric oxide
production, thereby enabling parasite survival. They also hamper the
cellular immune response by diminishing MHC-I and CD86 on an important
antigen-presenting cell, which potentially interferes with CD8 T cell
activation. The enhanced CD1d expression in combination with reduction
of PD-L1 on BMMs point to a potential shift of the activation route
towards lipid presentations, yet the effectivity of this immune
activation is not evident, since in the absence of costimulatory
molecules, cellular anergy and tolerance would be expected.
Filiaciones:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Invest Med Expt, Dr Balmis 148, Ciudad De Mexico 06726, Mexico
Univ Nacl Autonoma Mexico, Fac Med Vet & Zootecnia, Dept Patol & Microscopia Elect, Circuito Exterior, Ciudad Univ,Av Univ 3000, Ciudad De Mexico 04510, Mexico
Inst Nacl Cardiol Ignacio Chavez, Unidad Invest UNAM INC, Div Invest, Fac Med, Juan Badiano 1,Col Sect 16, Ciudad De Mexico 14080, Mexico
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