Complement Interaction with Trypanosomatid Promastigotes in Normal Human Serum
Open Access
- 18 February 2002
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 195 (4) , 451-459
- https://doi.org/10.1084/jem.20011319
Abstract
In normal human serum (NHS), axenic promastigotes of Crithidia, Phytomonas, and Leishmania trigger complement activation, and from 1.2 to 1.8 × 105 C3 molecules are deposited per promastigote within 2.5 min. In Leishmania, promastigote C3 binding capacity remains constant during in vitro metacyclogenesis. C3 deposition on promastigotes activated through the classical complement pathway reaches a 50% maximum after ∼50 s, and represents >85% of total C3 bound. In C1q- and C2-deficient human sera, promastigotes cannot activate the classical pathway (CP) unless purified C1q or C2 factors, respectively, are supplemented, demonstrating a requirement for CP factor in promastigote C3 opsonization. NHS depleted of natural anti-Leishmania antibodies cannot trigger promastigote CP activation, but IgM addition restores C3 binding. Furthermore, Leishmania binds natural antibodies in ethylenediaminetetracetic acid (EDTA)-treated NHS; after EDTA removal, promastigote-bound IgM triggers C3 deposition in natural antibody-depleted NHS. Serum collectins and pentraxins thus do not participate significantly in NHS promastigote C3 opsonization. Real-time kinetic analysis of promastigote CP-mediated lysis indicates that between 85–95% of parasites are killed within 2.5 min of serum contact. These data indicate that successful Leishmania infection in man must immediately follow promastigote transmission, and that Leishmania evasion strategies are shaped by the selective pressure exerted by complement.Keywords
This publication has 43 references indexed in Scilit:
- Mannan-Binding Lectin Enhances Susceptibility to Visceral LeishmaniasisInfection and Immunity, 2001
- Leishmania virulence: it's a knock out!Trends in Parasitology, 2001
- C-type lectin-like domainsPublished by Elsevier ,1999
- Immune Adherence–mediated Opsonophagocytosis: The Mechanism of Leishmania InfectionThe Journal of Experimental Medicine, 1999
- Leishmania, macrophages and complement: a tale of subversion and exploitationParasitology, 1997
- The concentration of the C-type lectin, mannan-binding protein, in human plasma increases during an acute phase responseClinical and Experimental Immunology, 1992
- Leishmania promastigotes require opsonic complement to bind to the human leukocyte integrin Mac-1 (CD11b/CD18).The Journal of cell biology, 1992
- Complement binding by two developmental stages of Leishmania major promastigotes varying in expression of a surface lipophosphoglycan.The Journal of Experimental Medicine, 1988
- C-REACTIVE PROTEIN FIFTY YEARS ONThe Lancet, 1981