Article
Antibodies to variable surface antigens induce antigenic variation in the intestinal parasite Giardia lamblia
Registro en:
TENAGLIA, Albano H. et al. Antibodies to variable surface antigens induce antigenic variation in the intestinal parasite Giardia lamblia. Nature Communications, v. 14:2537, p. 1 - 13, May 2023.
2041-1723
10.1038/s41467-023-38317-8
Autor
Tenaglia, Albano H.
Luján, Lucas A.
Rios, Diego N.
Molina, Cecilia R.
Midlej, Victor
Iribarren Paula A.
Berazategui, Maria A.
Torri, Alessandro
Saura, Alicia
Peralta, Damián O.
Rodríguez-Walker, Macarena
Fernández, Elmer A.
Petiti, Juan P.
Serradell, Marianela C.
Gargantini, Pablo R.
Sparwasser, Tim
Alvarez, Vanina E.
Souza, Wanderley de
Luján, Hugo D.
Resumen
The genomes of most protozoa encode families of variant surface antigens. In
some parasitic microorganisms, it has been demonstrated that mutually
exclusive changes in the expression of these antigens allowparasites to evade
the host’s immune response. It is widely assumed that antigenic variation in
protozoan parasites is accomplished by the spontaneous appearance within
the population of cells expressing antigenic variants that escape antibodymediated
cytotoxicity. Here we show, both in vitro and in animal infections,
that antibodies to Variant-specific Surface Proteins (VSPs) of the intestinal
parasite Giardia lamblia are not cytotoxic, inducing instead VSP clustering into
liquid-ordered phase membrane microdomains that trigger a massive release
of microvesicles carrying the original VSP and switch in expression to different
VSPs by a calcium-dependent mechanism. This novel mechanism of surface
antigen clearance throughout its release into microvesicles coupled to the
stochastic induction of new phenotypic variants not only changes current
paradigms of antigenic switching but also provides a new framework for
understanding the course of protozoan infections as a host/parasite adaptive
process.