The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/1/25/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 1, January 4, 1999 25-35

Articles

Immune Adherence–mediated Opsonophagocytosis: The Mechanism of Leishmania Infection

Mercedes Domínguez and Alfredo Toraño

From the Servicio de Inmunología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, E-28220 Madrid, Spain

To mimic the sandfly pool feeding process and characterize the cellular and biochemical events that occur during the early stages of promastigote–host interaction, we developed an ex vivo model of human blood infection with Leishmania promastigotes. Within 30 s of blood contact, Leishmania promastigotes bind natural anti–Leishmania antibodies, which then activate the classical complement pathway and opsonization by the third component of complement. The opsonized promastigotes undergo an immune adherence reaction and bind quantitatively to erythrocyte CR1 receptors; opsonized Leishmania amastigotes also bind to erythrocytes. Progression of infection implies promastigote transfer from erythrocytes to acceptor blood leukocytes. After 10 min of ex vivo infection, 25% of all leukocytes contain intracellular parasites, indicating that blood cells are the early targets for the invading promastigotes. We propose that adaptation to the immune adherence mechanism aids Leishmania survival, promoting rapid promastigote phagocytosis by leukocytes. This facilitates host colonization and may represent the parasite's earliest survival strategy. In light of this mechanism, it is unlikely that infection-blocking vaccines can be developed.

Key Words: Leishmania • infection • immune adherence • natural antibodies • complement

Address correspondence to Alfredo Toraño, Servicio de Inmunología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, E-28220 Madrid, Spain. Phone: 34-91-509-7973; Fax: 34-91-509-7966; E-mail: atorano{at}isciii.es

1 Abbreviations used in this paper: Ads-NHS, adsorbed NHS; AET, 2-aminoethyl isothiouronium; AO, acridine orange; C3, the third component of complement; C3dg, degradation fragment of C3; CR, complement receptor; goat anti-µ, goat anti–human immunoglobulin µ chain; IA, immune adherence; iC3b, inactivated C3b; MA, methylamine hydrochloride; MN, mononuclear phagocyte; NHS, normal human serum; NMS, normal mouse serum; NRS, normal rabbit serum; PFS, PBS containing 2.5% FCS and 0.05% NaN3.


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