Discovery of Markers of Exposure Specific to Bites of Lutzomyia longipalpis, the Vector of Leishmania infantum chagasi in Latin America

Teixeira, Clarissa; Gomes, Régis; Collin, Nicolas; Reynoso, David; Jochim, Ryan C.; Oliveira, Fabiano; Seitz, Amy E.; Elnaiem, Dia-Eldin A.; Caldas, Arlene de Jesus Mendes; Souza, Ana Paula Duarte de; Brodskyn, Cláudia; Mendonça, Ivete Lopes de; Costa, Carlos Henrique Nery; Volf, Petr; Barral, Aldina; Kamhawi, Shaden; Valenzuela, Jesús G.

doi:10.1371/journal.pntd.0000638

Cited by 102 publications

(161 citation statements)

References 36 publications

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“…Thus, most IgG4 Abs from FS patients might be developed against this epitope. LJM11 is known to be the most immunogenic component in sand fly saliva (35) and it might be due to this cross-reactive epitope. In this regard, the cross-reactive epitope on Dsg1 must be a predominant epitope for the development of anti-Dsg1 Abs in FS.…”

Section: Discussionmentioning

confidence: 99%

“…Produced scFv mAbs were purified by either Nickel column (Qiagen, CA) or anti-FLAG magnetic beads (Sigma, MO) according to manufacturers’ instruction for further testing. Human Dsg1 and sand fly LJM11 protein were purified as described (13, 35, 36, 40, 43). …”

Section: Methodsmentioning

confidence: 99%

“…LJM11). The LJM11 antigen, a member of the “yellow family” of salivary proteins is one of the most immunogenic component among the sand fly saliva proteins and is also a marker for human exposure of sand fly bites (35). Given that anti-LJM11 Abs cross-react to autoantigen Dsg1 (13, 36) strongly suggests the existence of a “cross-reactive” epitope(s) on both LJM11 and Dsg1.…”

Section: Introductionmentioning

confidence: 99%

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Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus

Qian

Jeong

et al. 2016

The Journal of Immunology

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The etiology of human autoimmune diseases in general remains largely unknown, although the genetic and environmental interplay may be relevant. This applies to the autoimmune diseases of the skin such as the pemphigus phenotypes and others. In this group, there is an endemic form of pemphigus foliaceus [also known as Fogo Selvagem (FS)] where the pathogenic IgG4 autoantibody response to the self-antigen, Desmoglein 1 (Dsg1) cross-react with the LJM11 sand fly salivary gland antigen. In this investigation we dissected the IgG4 autoantibody repertoires utilized by FS patients in response to endogenous self Dsg1 and exogenous LJM11 sand fly antigen. Based on analyses of the genetic clonal signatures of these antibodies, our results indicate that there is a significant overlap between these two responses as all identified IgG4 monoclonal antibodies cross-react to both Dsg1 and LJM11 antigens. Germline H and L chain V gene antibodies generated according to mutated cross-reactive monoclonal antibodies preserved their reactivity to both antigens. Our findings suggest that both Dsg1 autoantigen and LJM11 environmental antigen could be the initial antigenic stimulants for the IgG4 autoimmune responses in FS. These results support our hypothesis that LJM11 antigen plays a substantial role in triggering the IgG4 autoantibody development in FS, and provide new insights on how non-infectious environmental antigen(s) may drive the generation of autoantibodies in IgG4-related autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus

Qian

Jeong

et al. 2016

The Journal of Immunology

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“…Lu. longipalpisis the main vector of visceral leishmaniasis in Latin America, mainly located in dry tropical forests, arid and semi-arid areas, but also there are reports in very humid and forest areas (22).…”

Section: Vectorsmentioning

confidence: 99%

Leishmaniasis visceral en América Latina y perspectivas terapéuticas

Yasnot

2017

Rev MVZ Córdoba

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In Latin America, visceral leishmaniasis is caused by Leishmania infantum. In this geographical area, main vectors associated with transmission are Lutzomyia longipalpis and Lutzomyia evansi, with dogs being incriminated as the main reservoir involved in transmission of the disease. This pathology primarily affects children between 0 -5 years, a highly susceptible population where socio-economic, environmental and nutritional factors affects the pathological outcome and increase the likelihood of vector-human contact. According to the World Health Organization (WHO) recommended treatment for Visceral Leishmaniasis is liposomal amphotericin B, a drug with a limited and variable availability between countries depending on market prices, which leaves pentavalent antimonial as the most widely used treatment despite the associated toxic effects. In the Americas, evidence on the efficacy of single-dose (monotherapy) and combination therapies as options for treating these parasites is required. Disease, drug therapy, Leishmania infantum, Lutzomyia, vector (Source: MeSH). Keywords: RESUMENLa Leishmaniasis visceral es una enfermedad causada en América Latina por Leishmania infantum, en esta área geográfica los principales vectores asociados a la transmisión son Lutzomyia longipalpis y Lutzomyia evansi, siendo el perro uno de los principales reservorios incriminados en su transmisión. Es una patología que afecta principalmente a la población infantil entre los 0 a 5 años, donde los factores socioeconómicos, ambientales y nutricionales son determinantes en el contacto con el insecto vector y el desenlace patológico. Según la Organización Mundial de la Salud el tratamiento recomendando para esta patología es la Anfotericina B liposomal, sin embargo, la disponibilidad del medicamento por el costo varía entre los diferentes países, dejando antimoniales pentavalentes como opción más utilizada, pese a los efectos tóxicos asociados. En el continente americano se requiere evidencia de la eficacia de monoterapias de una solo dosis y terapias combinadas, como opciones para el tratamiento de estas parasitosis. INTRODUCCIÓNLa Leishmaniasis visceral (LV) es una parasitosis causada por un protozoo flagelado del género Leishmania, en América Latina la especie responsable de esta forma clínica es Leishmania infantum, su ciclo de transmisión involucra un insecto vector perteneciente al género Lutzomyia, y animales reservorios, como el perro que se destaca por su papel en el ciclo de transmisión doméstica (1).El proceso infeccioso inicia cuando una hembra hematófaga del genero Lutzomyia se alimenta de sangre del hospedador liberando de sus glándulas salivares promastigotes metacíclicos, los cuales son fagocitados principalmente por macrófagos locales, al interior se transforman en amastigotes que se reproducen intracelularmente. Tras la ruptura del macrófago los amastigotes son liberados con la capacidad de infectar nuevas células, posteriormente migran al hígado, medula ósea y bazo (2) alterando la arquitectura esplénica y produc...

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“…These two proteins were also recognized by sera of dogs naturally exposed to Lu. longipalpis bites [40] and by sera of sentinel chickens [39]. …”

Section: The Use Of Insect Salivary Proteins As Biomarkers For Vectormentioning

confidence: 99%

Impact of insect salivary proteins in blood feeding, host immunity, disease, and in the development of biomarkers for vector exposure

Coutinho-Abreu

Guimarães-Costa

Valenzuela

2015

Current Opinion in Insect Science

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Functional genomic approaches based on expression of recombinant proteins linked to biochemical and disease model approaches resulted in the discovery of novel biological activities and the role some of these proteins play in disease transmission. Importantly, the expression of salivary proteins was recently shown to be affected by environmental factors and by the presence of the pathogen in the salivary gland. A practical application resulting from insect saliva research is the use of insect antigenic salivary protein as biomarkers of vector exposure in humans and animal reservoirs, an approach that is yielding interesting results in the field.

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Discovery of Markers of Exposure Specific to Bites of Lutzomyia longipalpis, the Vector of Leishmania infantum chagasi in Latin America

Cited by 102 publications

References 36 publications

Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus

Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus

Leishmaniasis visceral en América Latina y perspectivas terapéuticas

Impact of insect salivary proteins in blood feeding, host immunity, disease, and in the development of biomarkers for vector exposure

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