title: Delayed-type hypersensitivity to sand fly saliva in humans from a leishmaniasis-endemic area of Mali is Th1-mediated and persists to midlife.
abstract: Immunity to sand fly saliva in rodents induces a T(H)1 delayed-type hypersensitivity (DTH) response conferring protection against leishmaniasis. The relevance of DTH to sand fly bites in humans living in a leishmaniasis-endemic area remains unknown. Here, we describe the duration and nature of DTH to sand fly saliva in humans from an endemic area of Mali. DTH was assessed at 24, 48, 72, and 96 hours post bite in volunteers exposed to colony-bred sand flies. Dermal biopsies were obtained 48 hours post bite; cytokines were quantified from peripheral blood mononuclear cells (PBMCs) stimulated with sand fly saliva in vitro. A DTH response to bites was observed in 75% of individuals aged 1-15 years, decreasing gradually to 48% by age 45, and dropping to 21% thereafter. Dermal biopsies were dominated by T lymphocytes and macrophages. Abundant expression of IFN-γ and absence of T(H)2 cytokines establishes the T(H)1 nature of this DTH response. PBMCs from 98% of individuals responded to sand fly saliva. Of these, 23% were polarized to a T(H)1 and 25% to a T(H)2 response. We demonstrate the durability and T(H)1 nature of DTH to sand fly bites in humans living in a cutaneous leishmaniasis-endemic area. A systemic T(H)2 response may explain why some individuals remain susceptible to disease.
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research (LMVR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland, USA.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Oliveira
authors.forename: Bourama
authors.initials: B
authors.lastname: Traoré
authors.forename: Regis
authors.initials: R
authors.lastname: Gomes
authors.forename: Ousmane
authors.initials: O
authors.lastname: Faye
authors.forename: Dana C
authors.initials: DC
authors.lastname: Gilmore
authors.forename: Somita
authors.initials: S
authors.lastname: Keita
authors.forename: Pierre
authors.initials: P
authors.lastname: Traoré
authors.forename: Clarissa
authors.initials: C
authors.lastname: Teixeira
authors.forename: Cheick A
authors.initials: CA
authors.lastname: Coulibaly
authors.forename: Sibiry
authors.initials: S
authors.lastname: Samake
authors.forename: Claudio
authors.initials: C
authors.lastname: Meneses
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Sissoko
authors.forename: Rick M
authors.initials: RM
authors.lastname: Fairhurst
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Seydou
authors.initials: S
authors.lastname: Doumbia
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D001733:Bites and Stings / Q000276:immunology / Q000469:parasitology; D002648:Child; D004198:Disease Susceptibility / Q000453:epidemiology / Q000276:immunology; D019353:Endemic Diseases / Q000517:prevention & control / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology*; D018320:Leishmania major / Q000276:immunology*; D007896:Leishmaniasis / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D008302:Mali / Q000453:epidemiology; D008875:Middle Aged; D011576:Psychodidae / Q000276:immunology*; D012377:Rodentia; D012463:Saliva / Q000276:immunology*; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan