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.
J Invest Dermatol. 2013 Feb;133(2):452-9. doi: 10.1038/jid.2012.315. Epub 2012 Sep 20.
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.
沙蝇唾液中的免疫原性在啮齿动物中引起 T(H)1 迟发型超敏反应 (DTH)，从而对利什曼病提供保护。DTH 与生活在利什曼病流行地区的沙蝇叮咬之间的相关性在人类中尚不清楚。在这里，我们描述了来自马里一个利什曼病流行地区的人类对沙蝇唾液的 DTH 持续时间和性质。在暴露于群体饲养的沙蝇的志愿者中，在叮咬后 24、48、72 和 96 小时评估 DTH。在叮咬后 48 小时获得皮肤活检；从体外用沙蝇唾液刺激外周血单核细胞 (PBMC) 中定量细胞因子。在 1-15 岁的个体中观察到 75%的人对叮咬有 DTH 反应，到 45 岁时逐渐降至 48%，此后降至 21%。皮肤活检主要由 T 淋巴细胞和巨噬细胞组成。IFN-γ 的大量表达和 T(H)2 细胞因子的缺乏确立了这种 DTH 反应的 T(H)1 性质。98%的个体的 PBMC 对沙蝇唾液有反应。其中，23%被极化到 T(H)1 反应，25%被极化到 T(H)2 反应。我们证明了生活在皮肤利什曼病流行地区的人类对沙蝇叮咬的 DTH 具有耐久性和 T(H)1 性质。全身性 T(H)2 反应可能解释了为什么一些人仍然容易患病。
