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1. Leishmania genetic exchange is mediated by IgM natural antibodies

Author

Serafim, Tiago D., Iniguez, Eva, Barletta, Ana Beatriz F., Cecilio, Pedro, Doehl, Johannes S. P., Short, Mara, Lack, Justin, Nair, Vinod, Disotuar, Maria, Wilson, Timothy, Coutinho-Abreu, Iliano V., Meneses, Claudio, Andersen, John, Alves E Silva, Thiago Luiz, Oliveira, Fabiano, Vega-Rodriguez, Joel, Barillas-Mury, Carolina, Ribeiro, José M. C., Beverley, Stephen M., Kamhawi, Shaden, and Valenzuela, Jesus G.

Published
2023
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3. Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance

Author

DeSouza-Vieira, Thiago, Iniguez, Eva, Serafim, Tiago D., de Castro, Waldionê, Karmakar, Subir, Disotuar, Maria M., Cecilio, Pedro, Lacsina, Joshua R., Meneses, Claudio, Nagata, Bianca M., Cardoso, Silvia, Sonenshine, Daniel E., Moore, Ian N., Borges, Valeria M., Dey, Ranadhir, Soares, Miguel P., Nakhasi, Hira L., Oliveira, Fabiano, Valenzuela, Jesus G., and Kamhawi, Shaden

Published
2020
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9. A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing

Author

Zhang, Wen-Wei, Karmakar, Subir, Gannavaram, Sreenivas, Dey, Ranadhir, Lypaczewski, Patrick, Ismail, Nevien, Siddiqui, Abid, Simonyan, Vahan, Oliveira, Fabiano, Coutinho-Abreu, Iliano V., DeSouza-Vieira, Thiago, Meneses, Claudio, Oristian, James, Serafim, Tiago D., Musa, Abu, Nakamura, Risa, Saljoughian, Noushin, Volpedo, Greta, Satoskar, Monika, Satoskar, Sanika, Dagur, Pradeep K., McCoy, J. Philip, Kamhawi, Shaden, Valenzuela, Jesus G., Hamano, Shinjiro, Satoskar, Abhay R., Matlashewski, Greg, and Nakhasi, Hira L.

Published
2020
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12. A Composite Recombinant Salivary Proteins Biomarker for Phlebotomus argentipes Provides a Surveillance Tool Postelimination of Visceral Leishmaniasis in India

Author

Iniguez, Eva, primary, Saha, Samiran, additional, Petrellis, Georgios, additional, Menenses, Claudio, additional, Herbert, Samantha, additional, Gonzalez-Rangel, Yvonne, additional, Rowland, Tobin, additional, Aronson, Naomi E, additional, Rose, Clair, additional, Rafuse Haines, Lee, additional, Acosta-Serrano, Alvaro, additional, Serafim, Tiago D, additional, Oliveira, Fabiano, additional, Srikantiah, Sridhar, additional, Bern, Caryn, additional, Valenzuela, Jesus G, additional, and Kamhawi, Shaden, additional

Published
2022
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13. List of Contributors

Author

Andersen, John F., primary, Bonnet, Sarah, additional, Boulanger, Nathalie, additional, Caljon, Guy, additional, Costero-Saint Denis, Adriana, additional, Coutinho-Abreu, Iliano V., additional, de Castro, Waldionê, additional, De Trez, Carl, additional, Dey, Ranadhir, additional, Fikrig, Erol, additional, Higgs, Stephen, additional, Huang, Yan-Jang S., additional, Kamhawi, Shaden, additional, Kincaid, Randall, additional, Kotsyfakis, Michail, additional, W. Leitner, Wolfgang, additional, McClure, Erin E., additional, Nakhasi, Hira L., additional, Narasimhan, Sukanya, additional, Oliveira, Fabiano, additional, Pedra, Joao H.F., additional, Poinsignon, Anne, additional, Remoue, Franck, additional, Ribeiro, José M.C., additional, Sagna, Andre, additional, Schleicher, Tyler R., additional, Serafim, Tiago D., additional, Shaw, Dana K., additional, Stijlemans, Benoît, additional, Valenzuela, Jesus G., additional, Van Den Abbeele, Jan, additional, Vanlandingham, Dana L., additional, von Stebut, Esther, additional, Wali, Tonu, additional, and Wikel, Stephen, additional

Published
2017
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15. Genetic exchange in Leishmania is facilitated by IgM natural antibodies

Author

Serafim, Tiago D., primary, Iniguez, Eva, additional, Barletta, Ana Beatriz F., additional, Doehl, Johannes S.P., additional, Short, Mara, additional, Lack, Justin, additional, Cecilio, Pedro, additional, Nair, Vinod, additional, Disotuar, Maria, additional, Wilson, Timothy, additional, Coutinho-Abreu, Iliano V., additional, Oliveira, Fabiano, additional, Meneses, Claudio, additional, Barillas-Mury, Carolina, additional, Andersen, John, additional, Ribeiro, José M.C., additional, Beverley, Stephen M., additional, Kamhawi, Shaden, additional, and G.Valenzuela, Jesus, additional

Published
2022
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17. Leishmaniagenetic exchange is mediated by IgM natural antibodies

Author

Serafim, Tiago D., Iniguez, Eva, Barletta, Ana Beatriz F., Cecilio, Pedro, Doehl, Johannes S. P., Short, Mara, Lack, Justin, Nair, Vinod, Disotuar, Maria, Wilson, Timothy, Coutinho-Abreu, Iliano V., Meneses, Claudio, Andersen, John, Alves E Silva, Thiago Luiz, Oliveira, Fabiano, Vega-Rodriguez, Joel, Barillas-Mury, Carolina, Ribeiro, José M. C., Beverley, Stephen M., Kamhawi, Shaden, and Valenzuela, Jesus G.

Abstract

Host factors that mediate Leishmaniagenetic exchange are not well defined. Here we demonstrate that natural IgM (IgMn)1–4antibodies mediate parasite genetic exchange by inducing the transient formation of a spherical parasite clump that promotes parasite fusion and hybrid formation. We establish that IgMn from Leishmania-free animals binds to the surface of Leishmaniaparasites to induce significant changes in the expression of parasite transcripts and proteins. Leishmaniabinding to IgMn is partially lost after glycosidase treatment, although parasite surface phosphoglycans, including lipophosphoglycan, are not required for IgMn-induced parasite clumping. Notably, the transient formation of parasite clumps is essential for Leishmaniahybridization in vitro. In vivo, we observed a 12-fold increase in hybrid formation in sand flies provided a second blood meal containing IgMn compared with controls. Furthermore, the generation of recombinant progeny from mating hybrids and parental lines were only observed in sand flies provided with IgMn. Both in vitro and in vivo IgM-induced Leishmaniacrosses resulted in full genome hybrids that show equal patterns of biparental contribution. Leishmaniaco-option of a host natural antibody to facilitate mating in the insect vector establishes a new paradigm of parasite–host–vector interdependence that contributes to parasite diversity and fitness by promoting genetic exchange.

Published
2023
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20. Gut Microbes Egested during Bites of Infected Sand Flies Augment Severity of Leishmaniasis via Inflammasome-Derived IL-1β

Author

Dey, Ranadhir, Joshi, Amritanshu B., Oliveira, Fabiano, Pereira, Lais, Guimarães-Costa, Anderson B., Serafim, Tiago D., de Castro, Waldionê, Coutinho-Abreu, Iliano V., Bhattacharya, Parna, Townsend, Shannon, Aslan, Hamide, Perkins, Alec, Karmakar, Subir, Ismail, Nevien, Karetnick, Morgan, Meneses, Claudio, Duncan, Robert, Nakhasi, Hira L., Valenzuela, Jesus G., and Kamhawi, Shaden

Published
2018
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21. Heme Oxygenase-1 Induction by Blood Feeding Arthropods Controls Skin Inflammation and Promotes Tolerance to Pathogens

Author

DeSouza-Vieira, Thiago, primary, Iniguez, Eva, additional, Serafim, Tiago D., additional, de Castro, Waldionê, additional, Karmakar, Subir, additional, Disotuar, Maria M., additional, Cecilio, Pedro, additional, Lacsina, Joshua R., additional, Meneses, Claudio, additional, Nagata, Bianca M., additional, Cardoso, Silvia, additional, Sonenshine, Daniel E., additional, Moore, Ian N., additional, Borges, Valeria M., additional, Dey, Ranadhir, additional, Soares, Miguel, additional, Nakhasi, Hira, additional, Oliveira, Fabiano, additional, Valenzuela, Jesus G., additional, and Kamhawi, Shaden, additional

Published
2020
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25. RNAi screening identifies Trypanosoma brucei stress response protein kinases required for survival in the mouse

Author

Fernandez-Cortes, Fernando, Serafim, Tiago D., Wilkes, Jonathan M., Jones, Nathaniel G., Ritchie, Ryan, McCulloch, Richard, and Mottram, Jeremy C.

Subjects
Genes, Essential, Sequence Analysis, RNA, Virulence Factors, Science, Trypanosoma brucei brucei, Protozoan Proteins, Article, Mice, Trypanosomiasis, African, polycyclic compounds, Medicine, Animals, RNA Interference, Protein Kinases, Signal Transduction
Abstract

Protein kinases (PKs) are a class of druggable targets in Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (sleeping sickness), yet little is known about which PKs are essential for survival in mammals. A recent kinome-wide RNAi screen with 176 individual bloodstream form Trypanosoma brucei lines identified PKs required for proliferation in culture. In order to assess which PKs are also potential virulence factors essential in vivo, lines were pooled, inoculated into mice, and screened for loss of fitness after 48 h RNAi. The presence of trypanosomes in the bloodstream was assessed using RNAi target sequencing (RITseq) and compared to growth in culture. We identified 49 PKs with a significant loss of fitness in vivo in two independent experiments, and a strong correlation between in vitro and in vivo loss of fitness for the majority. Nine PKs had a more pronounced growth defect in vivo, than in vitro. Amongst these PKs were several with putative functions related to stress responses mediated through the PI3K/TOR or MAPK signaling cascades, which act to protect the parasite from complement-mediated and osmotic lysis. Identification of these virulence-associated PKs provides new insights into T. brucei-host interaction and reveals novel potential protein kinase drug targets.

Published
2017

26. Gut Microbiota Egested During Bites of Infected Sand flies Augments Severity of Leishmaniasis via Inflammasome-Derived IL-11

Author

Dey, Ranadhir, primary, Joshi, Amritanshu B., additional, Oliveira, Fabiano, additional, Pereira, Lais, additional, Guimarres-Costa, Anderson B., additional, Serafim, Tiago D., additional, de Castro, Waldionn, additional, Coutinho-Abreu, Iliano V., additional, Bhattacharya, Parna, additional, Townsend, Shannon, additional, Aslan, Hamide, additional, Perkins, Alec, additional, Meneses, Claudio, additional, Duncan, Robert, additional, Nakhasi, Hira L., additional, Valenzuela, Jesus G., additional, and Kamhawi, Shaden, additional

Published
2018
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27. Genome-wide and protein kinase-focused RNAi screens reveal conserved and novel damage response pathways in Trypanosoma brucei

Author

Stortz, Jennifer A., primary, Serafim, Tiago D., additional, Alsford, Sam, additional, Wilkes, Jonathan, additional, Fernandez-Cortes, Fernando, additional, Hamilton, Graham, additional, Briggs, Emma, additional, Lemgruber, Leandro, additional, Horn, David, additional, Mottram, Jeremy C., additional, and McCulloch, Richard, additional

Published
2017
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29. Ecto-Nucleotidase Activities of Promastigotes from Leishmania (Viannia) braziliensis Relates to Parasite Infectivity and Disease Clinical Outcome

Author

Leite, Pauline M., primary, Gomes, Rodrigo S., additional, Figueiredo, Amanda B., additional, Serafim, Tiago D., additional, Tafuri, Wagner L., additional, de Souza, Carolina C., additional, Moura, Sandra A. L., additional, Fietto, Juliana L. R., additional, Melo, Maria N., additional, Ribeiro-Dias, Fátima, additional, Oliveira, Milton A. P., additional, Rabello, Ana, additional, and Afonso, Luís C. C., additional

Published
2012
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31. Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A2B adenosine receptor activation.

Author

Figueiredo, Amanda B., Serafim, Tiago D., Marques-da-Silva, Eduardo A., Meyer-Fernandes, José R., and Afonso, Luís C. C.

Abstract

Dendritic cells ( DCs) play an essential role in the modulation of immune responses and several studies have evaluated the interactions between Leishmania parasites and DCs. While extracellular ATP exhibits proinflammatory properties, adenosine is an important anti-inflammatory mediator. Here we investigated the effects of Leishmania infection on DC responses and the participation of purinergic signalling in this process. Bone marrow-derived dendritic cells ( BMDCs) from C57 BL/6 J mice infected with Leishmania amazonensis, Leishmania braziliensis or Leishmania major metacyclic promastigotes showed decreased major histocompatibility complex ( MHC) class II and CD86 expression and increased ectonucleotidase expression as compared with uninfected cells. In addition, L. amazonensis-infected DCs, which had lower CD40 expression, exhibited a decreased ability to induce T-cell proliferation. The presence of MRS1754, a highly selective A2B adenosine receptor antagonist at the time of infection increased MHC class II, CD86 and CD40 expression in L. amazonensis-infected DCs and restored the ability of the infected DCs to induce T-cell proliferation. Similar results were obtained through the inhibition of extracellular ATP hydrolysis using suramin. In conclusion, we propose that A2B receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response. [ABSTRACT FROM AUTHOR]

Published
2012
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32. The Gut Microbiome of the Vector Lutzomyia longipalpisIs Essential for Survival of Leishmania infantum

Author

Kelly, Patrick H., Bahr, Sarah M., Serafim, Tiago D., Ajami, Nadim J., Petrosino, Joseph F., Meneses, Claudio, Kirby, John R., Valenzuela, Jesus G., Kamhawi, Shaden, and Wilson, Mary E.

Abstract

ABSTRACTThe vector-borne disease leishmaniasis, caused by Leishmaniaspecies protozoa, is transmitted to humans by phlebotomine sand flies. Development of Leishmaniato infective metacyclic promastigotes in the insect gut, a process termed metacyclogenesis, is an essential prerequisite for transmission. Based on the hypothesis that vector gut microbiota influence the development of virulent parasites, we sequenced midgut microbiomes in the sand fly Lutzomyia longipalpiswith or without Leishmania infantuminfection. Sucrose-fed sand flies contained a highly diverse, stable midgut microbiome. Blood feeding caused a decrease in microbial richness that eventually recovered. However, bacterial richness progressively decreased in L. infantum-infected sand flies. Acetobacteraceaespp. became dominant and numbers of Pseudomonadaceaespp. diminished coordinately as the parasite underwent metacyclogenesis and parasite numbers increased. Importantly, antibiotic-mediated perturbation of the midgut microbiome rendered sand flies unable to support parasite growth and metacyclogenesis. Together, these data suggest that the sand fly midgut microbiome is a critical factor for Leishmaniagrowth and differentiation to its infective state prior to disease transmission.IMPORTANCELeishmania infantum, a parasitic protozoan causing fatal visceral leishmaniasis, is transmitted to humans through the bite of the sand fly Lutzomyia longipalpis. Development of the parasite to its virulent metacyclic state occurs in the sand fly gut. In this study, the microbiota within the Lu. longipalpismidgut was delineated by 16S ribosomal DNA (rDNA) sequencing, revealing a highly diverse community composition that lost diversity as parasites developed to their metacyclic state and increased in abundance in infected flies. Perturbing sand fly gut microbiota with an antibiotic cocktail, which alone had no effect on either the parasite or the fly, arrested both the development of virulent parasites and parasite expansion. These findings indicate the importance of bacterial commensals within the insect vector for the development of virulent pathogens, and raise the possibility that impairing the microbial composition within the vector might represent a novel approach to control of vector-borne diseases.

Published
2017
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33. Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A2B adenosine receptor activation.

Author

Figueiredo AB, Serafim TD, Marques-da-Silva EA, Meyer-Fernandes JR, and Afonso LC

Subjects
Acetamides pharmacology, Adenosine A2 Receptor Antagonists pharmacology, Animals, B7-2 Antigen biosynthesis, B7-2 Antigen immunology, Bone Marrow Cells immunology, CD40 Antigens biosynthesis, Cells, Cultured, Histocompatibility Antigens Class II immunology, Lymphocyte Activation immunology, Mice, Mice, Inbred C57BL, Nucleotidases biosynthesis, Purines pharmacology, Suramin pharmacology, T-Lymphocytes immunology, Trypanocidal Agents pharmacology, CD40 Antigens immunology, Dendritic Cells immunology, Leishmania immunology, Leishmaniasis immunology, Receptor, Adenosine A2B immunology
Abstract

Dendritic cells (DCs) play an essential role in the modulation of immune responses and several studies have evaluated the interactions between Leishmania parasites and DCs. While extracellular ATP exhibits proinflammatory properties, adenosine is an important anti-inflammatory mediator. Here we investigated the effects of Leishmania infection on DC responses and the participation of purinergic signalling in this process. Bone marrow-derived dendritic cells (BMDCs) from C57BL/6J mice infected with Leishmania amazonensis, Leishmania braziliensis or Leishmania major metacyclic promastigotes showed decreased major histocompatibility complex (MHC) class II and CD86 expression and increased ectonucleotidase expression as compared with uninfected cells. In addition, L. amazonensis-infected DCs, which had lower CD40 expression, exhibited a decreased ability to induce T-cell proliferation. The presence of MRS1754, a highly selective A(2B) adenosine receptor antagonist at the time of infection increased MHC class II, CD86 and CD40 expression in L. amazonensis-infected DCs and restored the ability of the infected DCs to induce T-cell proliferation. Similar results were obtained through the inhibition of extracellular ATP hydrolysis using suramin. In conclusion, we propose that A(2B) receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2012
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