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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #70416
Title: LEISHMANIA MAJOR-HUMAN MACROPHAGE INTERACTIONS: COOPERATION BETWEEN MAC-1 (CD11B/CD18) AND COMPLEMENT RECEPTOR TYPE 1 (CD35) IN PROMASTIGOTE ADHESION

Author
item ROSENTHAL, LOUIS - FDA; BETHESDA, MD
item SUTTERWALA, FAYYAZ - TEMPLE UNIV. PHILADELPHIA
item Kehrli Jr, Marcus
item MOSSER, DAVID - TEMPLE UNIV. PHILADELPHIA

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/9/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Leishmaniasis is usually a localized skin disease caused by a protozoan parasite spread to animals and humans by sandflies. An increasing frequency of international travel by US residents and the influx of immigrants into the US from endemic areas have resulted in increased numbers of cases presented to physicians in the United States. Research reported here identifies the major mechanism by which this parasite is eaten by a family of white blood cells, known as macrophages or monocytes. Our bovine model of leukocyte adhesion deficiency provided monocytes that conclusively demonstrated that a particular protein on white blood cells (known as CR3) is the primary receptor macrophages used to ingest the developmental stage of Leishmania major (the major species diagnosed in US patients). The main benefit of this work is the expansion of basic immunology knowledge that can now be exploited in the study of this rare disease.

Technical Abstract: It has been suggested that the developmental maturation of Leishmania major promastigotes can affect their interaction with human complement receptors. To study this, we measured the adhesion of metacyclic and logarithmic-phase L. major promastigotes to complement receptors expressed on primary macrophages, to recombinant receptors expressed on transfected cells, or to purified complement receptors in a cell-free system. We demonstrate that complement-opsonized promastigotes can bind to both Mac-1 and complement receptor type 1 (CR1), and that the transition of promastigotes from the noninfectious logarithmic phase of growth to the infectious metacyclic stage does not affect this interaction. Furthermore, we show that Mac-1 and CR1 can cooperate to mediate the efficient adhesion of complement-opsonized metacyclic promastigotes to cells expressing both receptors. On human monocyte-derived macrophages, Mac-1 appears to make a quantitatively greater contribution to this adhesion than does CR1, since blocking macrophage Mac-1 diminishes metacyclic promastigote adhesion to a greater extent than does blocking CR1. In addition, bovine monocytes lacking Mac-1 exhibit a dramatic decrease in complement-dependent promastigote adhesion, relative to normal monocytes.