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 TH1 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 96hours post bite in volunteers exposed to colony-bred sand flies. Dermal biopsies were obtained 48hours 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 TH2 cytokines establishes the TH1 nature of this DTH response. PBMCs from 98% of individuals responded to sand fly saliva. Of these, 23% were polarized to a TH1 and 25% to a TH2 response. We demonstrate the durability and TH1 nature of DTH to sand fly bites in humans living in a cutaneous leishmaniasis-endemic area. A systemic TH2 response may explain why some individuals remain susceptible to disease. Immunity to sand fly saliva in rodents induces a TH1 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 96hours post bite in volunteers exposed to colony-bred sand flies. Dermal biopsies were obtained 48hours 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 TH2 cytokines establishes the TH1 nature of this DTH response. PBMCs from 98% of individuals responded to sand fly saliva. Of these, 23% were polarized to a TH1 and 25% to a TH2 response. We demonstrate the durability and TH1 nature of DTH to sand fly bites in humans living in a cutaneous leishmaniasis-endemic area. A systemic TH2 response may explain why some individuals remain susceptible to disease. cutaneous leishmaniasis delayed-type hypersensitivity interferon gamma immediate-type hypersensitivity peripheral blood mononuclear cells salivary gland homogenate tumor growth factor-beta tumor necrosis factor T cell helper type 1