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

Abdeladhim, Maha; Kamhawi, Shaden; Valenzuela, Jesús G.

doi:10.1016/j.meegid.2014.07.028

Cited by 125 publications

(139 citation statements)

References 90 publications

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“…intermedia saliva [43], indicating that common antigens may exist across different species. Collectively, these studies highlight differences in salivary components [37], as mentioned before. They also reinforce the need to invest in characterizing salivary components and to perform systematic experiments to identify cross protective antigens.…”

Section: Discussionmentioning

confidence: 66%

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Immunity to Lutzomyia whitmani Saliva Protects against Experimental Leishmania braziliensis Infection

et al. 2016

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BackgroundPrevious works showed that immunization with saliva from Lutzomyia intermedia, a vector of Leishmania braziliensis, does not protect against experimental infection. However, L. braziliensis is also transmitted by Lutzomyia whitmani, a sand fly species closely related to Lu. intermedia. Herein we describe the immune response following immunization with Lu. whitmani saliva and the outcome of this response after L. braziliensis infection.Methods and findingsBALB/c mice immunized with Lu. whitmani saliva developed robust humoral and cellular immune responses, the latter characterized by an intense cellular infiltrate and production of IFN-γ and IL-10, by both CD4+ and CD8+ cells. Mice immunized as above and challenged with L. braziliensis plus Lu. whitmani saliva displayed significantly smaller lesions and parasite load at the challenge site. This protection was associated with a higher (p<0.05) IFN-γ production in response to SLA stimulation. Long-term persisting immunity was also detected in mice immunized with Lu. whitmani saliva. Furthermore, individuals residing in an endemic area for cutaneous leishmaniasis (CL) presented antibody responses to Lu. whitmani saliva. However CL patients, with active lesions, displayed a lower humoral response to Lu. whitmani saliva compared to individuals with subclinical Leishmania infection.ConclusionPre-exposure to Lu. whitmani saliva induces protection against L. braziliensis in a murine model. We also show that Lu. whitmani salivary proteins are immunogenic in naturally exposed individuals. Our results reinforce the importance of investigating the immunomodulatory effect of saliva from different species of closely related sand flies.

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Section: Discussionmentioning

confidence: 66%

“…papatasi , respectively. We suggest that these discrepancies maybe related to differences in salivary components among these species [37]. …”

Section: Discussionmentioning

confidence: 99%

Immunity to Lutzomyia whitmani Saliva Protects against Experimental Leishmania braziliensis Infection

et al. 2016

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“…Thereafter, parasites can benefit from this by means of vector saliva–altered site (reviewed in [27]).…”

Section: Effect Of Saliva On Leishmaniasismentioning

confidence: 99%

Insights into the sand fly saliva: Blood-feeding and immune interactions between sand flies, hosts, and Leishmania

et al. 2017

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BackgroundLeishmaniases are parasitic diseases present worldwide that are transmitted to the vertebrate host by the bite of an infected sand fly during a blood feeding. Phlebotomine sand flies inoculate into the mammalian host Leishmania parasites embedded in promastigote secretory gel (PSG) with saliva, which is composed of a diverse group of molecules with pharmacological and immunomodulatory properties.Methods and findingsIn this review, we focus on 3 main aspects of sand fly salivary molecules: (1) structure and composition of salivary glands, including the properties of salivary molecules related to hemostasis and blood feeding, (2) immunomodulatory properties of salivary molecules and the diverse impacts of these molecules on leishmaniasis, ranging from disease exacerbation to vaccine development, and (3) use of salivary molecules for field applications, including monitoring host exposure to sand flies and the risk of Leishmania transmission. Studies showed interesting differences between salivary proteins of Phlebotomus and Lutzomyia species, however, no data were ever published on salivary proteins of Sergentomyia species.ConclusionsIn the last 15 years, numerous studies have characterized sand fly salivary proteins and, in parallel, have addressed the impact of such molecules on the biology of the host–sand fly–parasite interaction. The results obtained shall pave the way for the development of field-application tools that could contribute to the management of leishmaniasis in endemic areas.

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“…platelet activation, coagulation, inflammation, mast cell function, and vasoconstriction (reviewed in [1]). In sand flies, the vectors of Leishmania protozoan parasites, these salivary proteins have been studied for decades due to their biological activities and possible use in anti- Leishmania vaccines (reviewed in [2]). In repeatedly bitten hosts, several salivary proteins elicit a strong antibody response, which can be utilized for the detection of exposure to sand flies in epidemiological studies [3–7].…”

Section: Introductionmentioning

confidence: 99%

The Diversity of Yellow-Related Proteins in Sand Flies (Diptera: Psychodidae)

Šíma¹,

Novotný²,

Pravda³

et al. 2016

PLoS ONE

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Yellow-related proteins (YRPs) present in sand fly saliva act as affinity binders of bioamines, and help the fly to complete a bloodmeal by scavenging the physiological signals of damaged cells. They are also the main antigens in sand fly saliva and their recombinant form is used as a marker of host exposure to sand flies. Moreover, several salivary proteins and plasmids coding these proteins induce strong immune response in hosts bitten by sand flies and are being used to design protecting vaccines against Leishmania parasites. In this study, thirty two 3D models of different yellow-related proteins from thirteen sand fly species of two genera were constructed based on the known protein structure from Lutzomyia longipalpis. We also studied evolutionary relationships among species based on protein sequences as well as sequence and structural variability of their ligand-binding site. All of these 33 sand fly YRPs shared a similar structure, including a unique tunnel that connects the ligand-binding site with the solvent by two independent paths. However, intraspecific modifications found among these proteins affects the charges of the entrances to the tunnel, the length of the tunnel and its hydrophobicity. We suggest that these structural and sequential differences influence the ligand-binding abilities of these proteins and provide sand flies with a greater number of YRP paralogs with more nuanced answers to bioamines. All these characteristics allow us to better evaluate these proteins with respect to their potential use as part of anti-Leishmania vaccines or as an antigen to measure host exposure to sand flies.

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

Cited by 125 publications

References 90 publications

Immunity to Lutzomyia whitmani Saliva Protects against Experimental Leishmania braziliensis Infection

Immunity to Lutzomyia whitmani Saliva Protects against Experimental Leishmania braziliensis Infection

Insights into the sand fly saliva: Blood-feeding and immune interactions between sand flies, hosts, and Leishmania

The Diversity of Yellow-Related Proteins in Sand Flies (Diptera: Psychodidae)

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