Dataset Information

Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America.

ABSTRACT: Sand flies deliver Leishmania parasites to a host alongside salivary molecules that affect infection outcomes. Though some proteins are immunogenic and have potential as markers of vector exposure, their identity and vector specificity remain elusive.We screened human, dog, and fox sera from endemic areas of visceral leishmaniasis to identify potential markers of specific exposure to saliva of Lutzomyia longipalpis. Human and dog sera were further tested against additional sand fly species. Recombinant proteins of nine transcripts encoding secreted salivary molecules of Lu. longipalpis were produced, purified, and tested for antigenicity and specificity. Use of recombinant proteins corresponding to immunogenic molecules in Lu. longipalpis saliva identified LJM17 and LJM11 as potential markers of exposure. LJM17 was recognized by human, dog, and fox sera; LJM11 by humans and dogs. Notably, LJM17 and LJM11 were specifically recognized by humans exposed to Lu. longipalpis but not by individuals exposed to Lu. intermedia.Salivary recombinant proteins are of value as markers of vector exposure. In humans, LJM17 and LJM11 emerged as potential markers of specific exposure to Lu. longipalpis, the vector of Leishmania infantum chagasi in Latin America. In dogs, LJM17, LJM11, LJL13, LJL23, and LJL143 emerged as potential markers of sand fly exposure. Testing these recombinant proteins in large scale studies will validate their usefulness as specific markers of Lu. longipalpis exposure in humans and of sand fly exposure in dogs.

SUBMITTER: Teixeira C

PROVIDER: S-EPMC2843637 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America.

Teixeira Clarissa C Gomes Regis R Collin Nicolas N Reynoso David D Jochim Ryan R Oliveira Fabiano F Seitz Amy A Elnaiem Dia-Eldin DE Caldas Arlene A de Souza Ana Paula AP Brodskyn Cláudia I CI de Oliveira Camila Indiani CI Mendonca Ivete I Costa Carlos H N CH Volf Petr P Barral Aldina A Kamhawi Shaden S Valenzuela Jesus G JG

PLoS neglected tropical diseases 20100323 3

<h4>Background</h4>Sand flies deliver Leishmania parasites to a host alongside salivary molecules that affect infection outcomes. Though some proteins are immunogenic and have potential as markers of vector exposure, their identity and vector specificity remain elusive.<h4>Methodology/principal findings</h4>We screened human, dog, and fox sera from endemic areas of visceral leishmaniasis to identify potential markers of specific exposure to saliva of Lutzomyia longipalpis. Human and dog sera wer ...[more]

PMID: 20351786

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Project description:Despite the increasing number of studies concerning insect immunity, Lutzomyia longipalpis immune responses in the presence of Leishmania infantum chagasi infection has not been widely investigated. The few available studies analyzed the role of the Toll and IMD pathways involved in response against Leishmania and microbial infections. Nevertheless, effector molecules responsible for controlling sand fly infections have not been identified. In the present study we investigated the role a signal transduction pathway, the Transforming Growth Factor-beta (TGF-β) pathway, on the interrelation between L. longipalpis and L. i. chagasi. We identified an L. longipalpis homolog belonging to the multifunctional cytokine TGF-β gene family (LlTGF-β), which is closely related to the activin/inhibin subfamily and potentially involved in responses to infections. We investigated this gene expression through the insect development and in adult flies infected with L. i. chagasi. Our results showed that LlTGF-β was expressed in all L. longipalpis developmental stages and was upregulated at the third day post L. i. chagasi infection, when protein levels were also higher as compared to uninfected insects. At this point blood digestion is finished and parasites are in close contact with the insect gut. In addition, we investigated the role of LlTGF-β on L. longipalpis infection by L. i. chagasi using either gene silencing by RNAi or pathway inactivation by addition of the TGF-β receptor inhibitor SB431542. The blockage of the LlTGF-β pathway increased significantly antimicrobial peptides expression and nitric oxide levels in the insect gut, as expected. Both methods led to a decreased L. i. chagasi infection. Our results show that inactivation of the L. longipalpis TGF-β signal transduction pathway reduce L. i. chagasi survival, therefore suggesting that under natural conditions the parasite benefits from the insect LlTGF-β pathway, as already seen in Plamodium infection of mosquitoes.

Project description:BackgroundIn the life cycle of Leishmania within the alimentary canal of sand flies the parasites have to survive the hostile environment of blood meal digestion, escape the blood bolus and attach to the midgut epithelium before differentiating into the infective metacyclic stages. The molecular interactions between the Leishmania parasites and the gut of the sand fly are poorly understood. In the present work we sequenced five cDNA libraries constructed from midgut tissue from the sand fly Lutzomyia longipalpis and analyzed the transcripts present following sugar feeding, blood feeding and after the blood meal has been processed and excreted, both in the presence and absence of Leishmania infantum chagasi.ResultsComparative analysis of the transcripts from sugar-fed and blood-fed cDNA libraries resulted in the identification of transcripts differentially expressed during blood feeding. This included upregulated transcripts such as four distinct microvillar-like proteins (LuloMVP1, 2, 4 and 5), two peritrophin like proteins, a trypsin like protein (Lltryp1), two chymotrypsin like proteins (LuloChym1A and 2) and an unknown protein. Downregulated transcripts by blood feeding were a microvillar-like protein (LuloMVP3), a trypsin like protein (Lltryp2) and an astacin-like metalloprotease (LuloAstacin). Furthermore, a comparative analysis between blood-fed and Leishmania infected midgut cDNA libraries resulted in the identification of the transcripts that were differentially expressed due to the presence of Leishmania in the gut of the sand fly. This included down regulated transcripts such as four microvillar-like proteins (LuloMVP1,2, 4 and 5), a Chymotrypsin (LuloChym1A) and a carboxypeptidase (LuloCpepA1), among others. Upregulated midgut transcripts in the presence of Leishmania were a peritrophin like protein (LuloPer1), a trypsin-like protein (Lltryp2) and an unknown protein.ConclusionThis transcriptome analysis represents the largest set of sequence data reported from a specific sand fly tissue and provides further information of the transcripts present in the sand fly Lutzomyia longipalpis. This analysis provides the detailed information of molecules present in the midgut of this sand fly and the transcripts potentially modulated by blood feeding and by the presence of the Leishmania parasite. More importantly, this analysis suggests that Leishmania infantum chagasi alters the expression profile of certain midgut transcripts in the sand fly during blood meal digestion and that this modulation may be relevant for the survival and establishment of the parasite in the gut of the fly. Moreover, this analysis suggests that these changes may be occurring during the digestion of the blood meal and not afterwards.

Project description:In some transmission foci of Leishmania infantum in Brazil, Lutzomyia cruzi could be considered the main vector of this pathogen. In addition, L. cruzi is a permissive vector of L. amazonensis. Its geographical distribution seems to be restricted and limited to Cerrado and Pantanal biomes, which includes some areas in Brazil and Bolivia. Considering that predicting the distribution of the species involved in transmission cycles is an effective approach for assessing human disease risk, this study aims to predict the spatial distribution of L. cruzi using a multiscale ecological niche model based in both climate and habitat variables. Ecological niche modelling was used to identify areas in South America that are environmentally suitable for this particular vector species, but its presence is not recorded. Vector occurrence records were compiled from the literature, museum collections and Brazilian Health Departments. Bioclimatic variables, altitude, and land use and cover were used as predictors in five ecological niche model algorithms: BIOCLIM, generalised linear model (logistic regression), maximum entropy, random forests, and support vector machines. The vector occurs in areas where annual mean temperature values range from 21.76°C to 26.58°C, and annual total precipitation varies from 1005 mm and 2048 mm. Urban areas were most present around capture locations. The potential distribution area of L. cruzi according to the final ecological niche model spans Brazil and Bolivia in patches of suitable habitats inside a larger climatically favourable area. The bigger portion of this suitable area is located at Brazilian States of Mato Grosso do Sul and Mato Grosso. Our findings identified environmentally suitable areas for L. cruzi in regions without its known occurrence, so further field sampling of sand flies is recommended, especially in southern Goiás State, Mato Grosso do Sul (borders with Mato Grosso, São Paulo and Minas Gerais); and in Bolivian departments Santa Cruz and El Beni.

Project description:The sand fly Lutzomyia longipalpis is the main vector of Leishmania infantum in Brazil. Synthetic male-produced sex/aggregation pheromone co-located with micro-encapsulated λ-cyhalothrin in chicken sheds can significantly reduce canine infection and sand fly densities in a lure-and-kill strategy. In this study, we determined if insecticide-impregnated netting (IN) could replace insecticide residual spraying (IRS). We compared numbers of Lu. longipalpis attracted and killed in experimental and real chicken sheds baited with pheromone and treated with a 1 m2 area of either insecticide spray or netting. First, we compared both treatments in experimental sheds to control mortality established from light trap captures. We then compared the long-term killing effect of insecticide spray and netting, without renewal, in experimental sheds over a period of 16 weeks. Finally, a longitudinal intervention study in real chicken sheds compared the numbers and proportions of Lu. longipalpis collected and killed before and after application of both treatments. In Experiment 1, a higher proportion of males and females captured in IRS- and IN-treated sheds were dead at 24 h compared to controls (P < 0.05). No difference was found in the proportion of females killed in sheds treated with IN or IRS (P = 0.15). A slightly higher proportion of males were killed by IRS (100%) compared to IN (98.6%; P < 0.05). In Experiment 2, IN- and IRS-treated traps were equally effective at killing females (P = 0.21) and males (P = 0.08). However, IRS killed a significantly higher proportion of females and males after 8 (P < 0.05) and 16 (P < 0.05) weeks. In Experiment 3, there was no significant difference between treatments in the proportion of females killed before (P = 0.88) or after (P = 0.29) or males killed before (P = 0.76) or after (P = 0.73) intervention. Overall, initially the IN was as effective as IRS at killing female and male Lu. longipalpis in both experimental and real chicken sheds. However, the relative lethal effect of the IN deteriorated over time when stored under prevailing environmental conditions.

Dataset Information

Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America.

Publications

Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America.

Similar Datasets

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