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During a blood meal,  Lutzomyia intermedia  sand flies transmit  Leishmania braziliensis , a parasite causing tegumentary leishmaniasis. In experimental leishmaniasis, pre-exposure to saliva of most blood-feeding sand flies results in parasite establishment in absence of any skin damages in mice challenged with dermotropic  Leishmania  species together with saliva. In contrast, pre-immunization with  Lu. intermedia  salivary gland sonicate (SGS) results in enhanced skin inflammatory exacerbation upon co-inoculation of  Lu. intermedia  SGS and  L. braziliensis . These data highlight potential unique features of both  L. braziliensis  and  Lu. intermedia . In this study, we investigated the genes modulated by  Lu. intermedia  SGS immunization to understand their potential impact on the subsequent cutaneous immune response following inoculation of both SGS and  L. braziliensis . The cellular recruitment and global gene expression profile was analyzed in mice repeatedly inoculated or not with  Lu. intermedia . Microarray gene analysis revealed the upregulation of a distinct set of IFN-inducible genes, an immune signature not seen to the same extent in control animals. Of note this INF-inducible gene set was not induced in SGS pre-immunized mice subsequently co-inoculated with SGS and  L. braziliensis . These data suggest the parasite prevented the upregulation of this  Lu. intermedia  saliva-related immune signature. The presence of these IFN-inducible genes was further analyzed in peripheral blood mononuclear cells (PBMCs) sampled from uninfected human individuals living in a  L. braziliensis -endemic region of Brazil thus regularly exposed to  Lu. intermedia  bites. PBMCs were cultured in presence or absence of  Lu. intermedia  SGS. Using qRT-PCR we established that the IFN-inducible genes induced in the skin of SGS pre-immunized mice, were also upregulated by SGS in PBMCs from human individuals regularly exposed to  Lu. intermedia  bites, but not in PBMCs of control subjects. These data demonstrate that repeated exposure to  Lu. intermedia  SGS induces the expression of potentially host-protective IFN-inducible genes.

plos neglected tropical diseases

Repeated Exposure to Lutzomyia intermedia Sand Fly Saliva Induces Local Expression of Interferon-Inducible Genes Both at the Site of Injection in Mice and in Human Blood