The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 487K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Domínguez, M.
Right arrow Articles by Toraño, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Domínguez, M.
Right arrow Articles by Toraño, A.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Medline Plus Health Information
*Leishmaniasis
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© 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.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS