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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.

SUBMITTER: Oliveira F

PROVIDER: S-EPMC3529997 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Phlebotomine sand flies transmit many viral protozoan and bacterial pathogens of public health importance. Knowledge of the ecologic factors influencing their distribution at local scale can provide insights into disease epidemiology and avenues for targeted control. Animal sheds, termite mounds and houses are important peri-domestic and domestic habitats utilized by different sand flies as resting or breeding habitats. However, our knowledge for selection of these habitats by sand flies remains poor. Here, we tested the hypothesis that these habitat types harbor different composition of sand fly species and differ in their volatile chemistry that could influence sand fly selection. To achieve this, we employed CDC light traps following a cross-sectional survey to investigate the distribution of sand flies in the three habitats in an endemic site for leishmaniasis in Kenya. The study was carried out during the dry season, when sand flies are optimally abundant in 2018 and 2020. Sand fly abundance did not vary between the habitats, but species-specific differences in abundance was evident. Measures of sand fly community structure (Shannon diversity and richness) were highest in animal shed, followed by termite mound and lowest inside human dwelling (house). This finding indicates broader attraction of both sexes of sand flies and females of varying physiological states to animal sheds potentially used as breeding or resting sites, but also as a signal for host presence for a blood meal. Furthermore, gas chromatography-mass spectrometric analysis of volatiles collected from represented substrates associated with these habitats viz: human foot odor on worn socks (houses indoors), cow dung (animal sheds) and termite mounds (enclosed vent), revealed a total of 47 volatile organic compounds. Of these, 26, 35 and 16 were detected in human socks, cow dung and enclosed termite vent, respectively. Of these volatiles, 1-octen-3-ol, 6-methyl-5-hepten-2-one, α-pinene, benzyl alcohol, m-cresol, p-cresol and decanal, previously known as attractants for sandflies and other blood-feeding insects, were common to the habitats. Our results suggest that habitat volatiles may contribute to the composition of sand flies and highlight their potential for use in monitoring sand fly populations.

Project description:BackgroundThe sand fly Phlebotomus papatasi is an Old World vector of Leishmania major, the etiologic agent of zoonotic cutaneous leishmaniasis. This study describes the courtship behaviour of P. papatasi and compares it with that of Lutzomyia longipalpis, the New World vector of visceral leishmaniasis. Understanding the details of courtship behaviour in P. papatasi may help us to understand the role of sex pheromones in this important vector.ResultsP. papatasi courtship was found to start with the female touching the male, leading him to begin abdomen bending and wing flapping. Following a period of leg rubbing and facing, the male flaps his wings while approaching the female. The female then briefly flaps her wings in response, to indicate that she is willing to mate, thereby signaling the male to begin copulation. Male P. papatasi did not engage in parading behaviour, which is performed by male L. longipalpis to mark out individual territories during lekking (the establishment and maintenance of mating aggregations), or wing-flap during copulation, believed to function in the production of audio signals important to mate recognition. In P. papatasi the only predictor of mating success for males was previous copulation attempts and for females stationary wing-flapping. By contrast, male L. longipalpis mating success is predicted by male approach-flapping and semi-circling behaviour and for females stationary wing-flapping.ConclusionsThe results show that there are important differences between the mating behaviours of P. papatasi and L. longipalpis. Abdomen bending, which does not occur in L. longipalpis, may act in the release of sex pheromone from an as yet unidentified site in the male abdomen. In male L. longipalpis wing-flapping is believed to be associated with distribution of male pheromone. These different behaviours are likely to signify significant differences in how pheromone is used, an observation that is consistent with field and laboratory observations.

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Delayed-type hypersensitivity to sand fly saliva in humans from a leishmaniasis-endemic area of Mali is Th1-mediated and persists to midlife.

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