title: Distinct innate and acquired immune responses to Leishmania in putative susceptible and resistant human populations endemically exposed to L. (Viannia) panamensis infection.
abstract: Mechanisms of constitutive and acquired susceptibility/resistance to Leishmania Viannia panamensis (L. (V ) p.) were investigated in endemically exposed human populations presenting either recurrent disease (putative susceptible) or subclinical infection (clinically resistant). Cutaneous delayed type hypersensitivity response to leishmanin was significantly lower among individuals experiencing recurrent leishmaniasis than among those whose skin test converted without developing the disease. Monocyte derived macrophages from individuals with recurrent disease were more permissive in vitro to the entry of parasites than macrophages from subclinically infected individuals. In vitro proliferation of CD4 and CD8 T lymphocytes in response to intracellular amastigotes was significantly lower among individuals with a history of recurrent disease compared with subclinically infected individuals. Linear regression analyses revealed a strong direct relationship between the production of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 by peripheral blood mononuclear cells (PBMC) from resistant (subclinically infected) individuals and no correlation in the production of these cytokines by PBMC from individuals who experienced recurrent disease. The results provide evidence of differences in the innate and acquired responses to Leishmania according to the outcome of the natural infection. These findings support the feasibility of identifying the immunological bases of innate and acquired resistance through studies in naturally exposed human populations.
authors.affiliation: Unité d'Immunophysiologie et parasitisme intracellulaire, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: F
authors.initials: F
authors.lastname: Bosque
authors.forename: N G
authors.initials: NG
authors.lastname: Saravia
authors.forename: L
authors.initials: L
authors.lastname: Valderrama
authors.forename: G
authors.initials: G
authors.lastname: Milon
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000469:parasitology; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000276:immunology; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D018334:Leishmania guyanensis / Q000276:immunology*; D007897:Leishmaniasis, Mucocutaneous / Q000453:epidemiology / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000469:parasitology; D011994:Recombinant Proteins; D012008:Recurrence; D012307:Risk Factors; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D016753:Interleukin-10; D007371:Interferon-gamma