Repeated Sand Fly Bites of Infected BALB/c Mice Enhance the Development of Leishmania Lesions

Abstract

Sand fly saliva has considerable immunomodulatory effects onLeishmaniainfections in mammalian hosts. Studies on severalLeishmania– sand fly - host combinations have demonstrated that co-inoculation withLeishmaniaparasites enhances pathogenicity, while pre-exposure of hosts to sand fly bites provides significant protection against infection. However, the third scenario, the effect of sand fly saliva on parasite development in hosts infected before exposure to sand flies, remains an understudied aspect ofLeishmania–host–vector interaction. Here we studied the effect of exposure ofL. major-infected BALB/c mice to repeated sand fly bites. Mice infected intradermally with sand fly-derivedLeishmaniawere repeatedly bitten byPhlebotomus duboscqifemales every two weeks. The lesion development was recorded weekly for ten weeks post-infection and parasite load and distribution in various organs were testedpost mortemusing qPCR. Repeated sand fly bites significantly enhanced the development of cutaneous lesions; they developed faster and reached larger size than in unexposed mice. Multiple sand fly bites also increased parasites load in inoculated ears. On the other hand, the distribution of parasites in mice body and their infectiousness to vectors did not differ significantly between groups. Our study provides the first evidence that multiple and repeated exposures of infected BALB/c mice to sand fly bites significantly enhance the progress of local skin infection caused byLeishmania majorand increase tissue parasite load, but do not affect the visceralization of parasites. This finding appeals to adequate protection of infected humans from sand fly bites, not only to prevent transmission but also to prevent enlarged lesions.