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What's behind a sand fly bite? The profound effect of sand fly saliva on host hemostasis, inflammation and immunity.

ABSTRACT: Sand flies are blood-feeding insects and vectors of the Leishmania parasite. For many years, saliva of these insects has represented a gold mine for the discovery of molecules with anti-hemostatic and immuno-modulatory activities. Furthermore, proteins in sand fly saliva have been shown to be a potential vaccine against leishmaniasis and also markers of vector exposure. A bottleneck to progress in these areas of research has been the identification of molecules responsible for the observed activities and properties of saliva. Over the past decade, rapid advances in transcriptomics and proteomics resulted in the completion of a number of sialomes (salivary gland transcriptomes) and the expression of several recombinant salivary proteins from different species of sand fly vectors. This review will provide readers with a comprehensive update of recent advances in the characterization of these salivary molecules and their biological activities and offer insights pertaining to their protective effect against leishmaniasis and their potential as markers of vector exposure.

SUBMITTER: Abdeladhim M

PROVIDER: S-EPMC4562216 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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What's behind a sand fly bite? The profound effect of sand fly saliva on host hemostasis, inflammation and immunity.

Abdeladhim Maha M Kamhawi Shaden S Valenzuela Jesus G JG

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 20140810

Sand flies are blood-feeding insects and vectors of the Leishmania parasite. For many years, saliva of these insects has represented a gold mine for the discovery of molecules with anti-hemostatic and immuno-modulatory activities. Furthermore, proteins in sand fly saliva have been shown to be a potential vaccine against leishmaniasis and also markers of vector exposure. A bottleneck to progress in these areas of research has been the identification of molecules responsible for the observed activ ...[more]

PMID: 25117872

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Project description:BackgroundIn Mali, cutaneous leishmaniasis (CL) and filariasis are co-endemic. Previous studies in animal models of infection have shown that sand fly saliva enhance infectivity of Leishmania parasites in naïve hosts while saliva-specific adaptive immune responses may protect against cutaneous and visceral leishmaniasis. In contrast, the human immune response to Phlebotomus duboscqi (Pd) saliva, the principal sand fly vector in Mali, was found to be dichotomously polarized with some individuals having a Th1-dominated response and others having a Th2-biased response. We hypothesized that co-infection with filarial parasites may be an underlying factor that modulates the immune response to Pd saliva in endemic regions.Methodology/principal findingsTo understand which cell types may be responsible for polarizing human responses to sand fly saliva, we investigated the effect of salivary glands (SG) of Pd on human monocytes. To this end, elutriated monocytes were cultured in vitro, alone, or with SG, microfilariae antigen (MF ag) of Brugia malayi, or LPS, a positive control. The mRNA expression of genes involved in inflammatory or regulatory responses was then measured as were cytokines and chemokines associated with these responses. Monocytes of individuals who were not exposed to sand fly bites (mainly North American controls) significantly upregulated the production of IL-6 and CCL4; cytokines that enhance leishmania parasite establishment, in response to SG from Pd or other vector species. This selective inflammatory response was lost in individuals that were exposed to sand fly bites which was not changed by co-infection with filarial parasites. Furthermore, infection with filarial parasites resulted in upregulation of CCL22, a type-2 associated chemokine, both at the mRNA levels and by its observed effect on the frequency of recruited monocytes.Conclusions/significanceTogether, our data suggest that SG or recombinant salivary proteins from Pd alter human monocyte function by upregulating selective inflammatory cytokines.

Dataset Information

What's behind a sand fly bite? The profound effect of sand fly saliva on host hemostasis, inflammation and immunity.

Publications

What's behind a sand fly bite? The profound effect of sand fly saliva on host hemostasis, inflammation and immunity.

Similar Datasets

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