title: Leishmania promotes its own virulence by inducing expression of the host immune inhibitory ligand CD200.
abstract: Leishmania parasites infect macrophages, cells normally involved in innate defense against pathogens. Leishmania amazonensis and Leishmania major cause severe or mild disease, respectively, consistent with each parasite's ability to survive within activated macrophages. The mechanisms underlying increased virulence of L. amazonensis are mostly unknown. We show that L. amazonensis promotes its own survival by inducing expression of CD200, an immunoregulatory molecule that inhibits macrophage activation. L. amazonensis does not form typical nonhealing lesions in CD200(-/-) mice and cannot replicate in CD200(-/-) macrophages, an effect reversed by exogenous administration of soluble CD200-Fc. The less virulent L. major does not induce CD200 expression and forms small, self-healing lesions in both wild-type and CD200(-/-) mice. Notably, CD200-Fc injection transforms the course of L. major infection to one resembling L. amazonensis, with large, nonhealing lesions. CD200-dependent iNOS inhibition allows parasite growth in macrophages, identifying a mechanism for the increased virulence of L. amazonensis.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Cortez
authors.forename: Chau
authors.initials: C
authors.lastname: Huynh
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Fernandes
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Kennedy
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.forename: Norma W
authors.initials: NW
authors.lastname: Andrews
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006790:Host-Parasite Interactions; D006801:Humans; D007891:Leishmania / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D007896:Leishmaniasis / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000276:immunology; D014774:Virulence
chemical_list: D015703:Antigens, CD; D009569:Nitric Oxide; C042739:antigens, CD200