Sensitization to sand fly bite prevents cutaneous leishmaniasis

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Until recently, from both epidemiological and clinical perspectives, arthropods have been considered as little more than delivery systems for the pathogens that they carry. However, insofar as components of their saliva have been shown to modify the outcome of infection, an active modulation by arthropod vectors of disease transmission is starting to gain recognition. The disease most studied in this context is cutaneous leishmaniasis, which is transmitted exclusively by the bite of infectious sand flies. Kamhawi et al.1xProtection against cutaneous leishmaniasis resulting from bites of uninfected sand flies. Kamhawi, S et al. Science. 2000; 290: 1351–1354Crossref | PubMed | Scopus (190)See all References1 have now described a reproducible murine model of Leishmania major infection transmitted by its natural vector, Phlebotomus papatasi, in which the ear is the site of parasite inoculation. The respective lesion-healing and lesion-non-healing phenotypes of C57BL/6 and BALB/c mice that have proved a powerful tool for dissection of the T helper type 1 (Th1)/Th2 immunological paradigm, established using high-dose needle inocula, were maintained in fly-transmitted infections. demonstrated that prior exposure of bites of uninfected sand flies alone provides a significant degree of protection against L. major, sufficient to confer resistance subsequent biting by infected sand flies. For both BALB/c and C57BL/6 mice, prior exposure to P. papatasi bites resulted striking reduction in both the severity dermal lesions and the parasite load.The protective mechanism involves a strong delayed-type hypersensitivity reaction and production of interleukin (IL)-12 and interferon (IFN)-. at the bite site. The rapidly raised secretion of these cytokines might activate infected macrophages for killing while the infection is initially establishing and might also promote an early polarized Leishmania-specific Th1-type response that is the immunological hallmark of a healing infection. The molecular identity of the stimulus that triggers this protective response remains to be elucidated but is thought to be a component of Phlebotomus saliva. These findings are very relevant to leishmaniasis of humans, for which many individuals in endemic regions are exposed to the bites of Leishmania-free sand flies before receiving an infective bite. Thus, a person's exposure history to uninfected phlebotomines could influence their susceptibility to, and the severity of, infection. Moreover, salivary antigens might be effective components of vaccines against this and other vector-borne infectious diseases.