Antibodies to variable surface antigens induce antigenic variation in the intestinal parasite Giardia lamblia

TENAGLIA, ALBANO H.; LUJÁN, LUCAS A.; RÍOS, DIEGO N.; MOLINA, CECILIA R.; MIDLEJ, VICTOR; IRIBARREN, PAULA A.; BERAZATEGUI, MARÍA 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.; DE SOUZA, WANDERLEY; LUJÁN, HUGO D.

NATURE COMMUNICATIONS

Nature Portfolio

Lugar: London; Año: 2023 vol. 14

2041-1723

The genomes of most protozoa encode families of variant surface antigens. Insome parasitic microorganisms, it has been demonstrated that mutuallyexclusive changes in the expression of these antigens allowparasites to evadethe host’s immune response. It is widely assumed that antigenic variation inprotozoan parasites is accomplished by the spontaneous appearance withinthe population of cells expressing antigenic variants that escape antibodymediatedcytotoxicity. Here we show, both in vitro and in animal infections,that antibodies to Variant-specific Surface Proteins (VSPs) of the intestinalparasite Giardia lamblia are not cytotoxic, inducing instead VSP clustering intoliquid-ordered phase membrane microdomains that trigger a massive releaseof microvesicles carrying the original VSP and switch in expression to differentVSPs by a calcium-dependent mechanism. This novel mechanism of surfaceantigen clearance throughout its release into microvesicles coupled to thestochastic induction of new phenotypic variants not only changes currentparadigms of antigenic switching but also provides a new framework forunderstanding the course of protozoan infections as a host/parasite adaptiveprocess.