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3. 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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5. Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification

Author

Kolli, Surendra Kumar, Molina-Cruz, Alvaro, Araki, Tamasa, Geurten, Fiona J. A., Ramesar, Jai, Chevalley-Maurel, Severine, Kroeze, Hans J., Bezemer, Sascha, de Korne, Clarize, Withers, Roxanne, Raytselis, Nadia, El Hebieshy, Angela F., Kim, Robbert Q., Child, Matthew A., Kakuta, Soichiro, Hisaeda, Hajime, Kobayashi, Hirotaka, Annoura, Takeshi, Hensbergen, Paul J., Franke-Fayard, Blandine M., Barillas-Mury, Carolina, Scheeren, Ferenc A., and Janse, Chris J.

Published
2022

15. Immunity-Related Genes and Gene Families in Anopheles gambiae

Author

Christophides, George K., Zdobnov, Evgeny, Barillas-Mury, Carolina, Birney, Ewan, Blandin, Stephanie, Blass, Claudia, Brey, Paul T., Collins, Frank H., Danielli, Alberto, Dimopoulos, George, Hetru, Charles, Hoa, Ngo T., Hoffmann, Jules A., Kanzok, Stefan M., Letunic, Ivica, Levashina, Elena A., Loukeris, Thanasis G., Lycett, Gareth, Meister, Stephan, Michel, Kristin, Moita, Luis F., Müller, Hans-Michael, Osta, Mike A., Paskewitz, Susan M., Reichhart, Jean-Marc, Rzhetsky, Andrey, Troxler, Laurent, Vernick, Kenneth D., Vlachou, Dina, Volz, Jennifer, von Mering, Christian, Xu, Jiannong, Zheng, Liangbiao, Bork, Peer, and Kafatos, Fotis C.

Published
2002

16. Comparative Genome and Proteome Analysis of Anopheles gambiae and Drosophila melanogaster

Author

Zdobnov, Evgeny M., von Mering, Christian, Letunic, Ivica, Torrents, David, Suyama, Mikita, Copley, Richard R., Christophides, George K., Thomasova, Dana, Holt, Robert A., Subramanian, G. Mani, Mueller, Hans-Michael, Dimopoulos, George, Law, John H., Wells, Michael A., Birney, Ewan, Charlab, Rosane, Halpern, Aaron L., Kokoza, Elena, Kraft, Cheryl L., Lai, Zhongwu, Lewis, Suzanna, Louis, Christos, Barillas-Mury, Carolina, Nusskern, Deborah, Rubin, Gerald M., Salzberg, Steven L., Sutton, Granger G., Topalis, Pantelis, Wides, Ron, Wincker, Patrick, Yandell, Mark, Collins, Frank H., Ribeiro, Jose, Gelbart, William M., Kafatos, Fotis C., and Bork, Peer

Published
2002

20. The Aedes aegypti peritrophic matrix controls arbovirus vector competence through HPx1, a heme–induced peroxidase

Author

Talyuli, Octavio A. C., primary, Oliveira, Jose Henrique M., additional, Bottino-Rojas, Vanessa, additional, Silveira, Gilbert O., additional, Alvarenga, Patricia H., additional, Barletta, Ana Beatriz F., additional, Kantor, Asher M., additional, Paiva-Silva, Gabriela O., additional, Barillas-Mury, Carolina, additional, and Oliveira, Pedro L., additional

Published
2023
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32. Evolutionary Dynamics of Immune-Related Genes and Pathways in Disease-Vector Mosquitoes

Author

Waterhouse, Robert M., Kriventseva, Evgenia V., Meister, Stephan, Xi, Zhiyong, Alvarez, Kanwal S., Bartholomay, Lyric C., Barillas-Mury, Carolina, Bian, Guowu, Blandin, Stephanie, Christensen, Bruce M., Dong, Yuemei, Jiang, Haobo, Kanost, Michael R., Koutsos, Anastasios C., Levashina, Elena A., Li, Jianyong, Ligoxygakis, Petros, MacCallum, Robert M., Mayhew, George F., Mendes, Antonio, Michel, Kristin, Osta, Mike A., Paskewitz, Susan, Shin, Sang Woon, Vlachou, Dina, Wang, Lihui, Wei, Weiqi, Zheng, Liangbiao, Zou, Zhen, Severson, David W., Raikhel, Alexander S., Kafatos, Fotis C., Dimopoulos, George, Zdobnov, Evgeny M., and Christophides, George K.

Published
2007
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34. Protective effects of combining monoclonal antibodies and vaccines against the Plasmodium falciparum circumsporozoite protein

Author

Wang, Lawrence T., primary, Pereira, Lais S., additional, Kiyuka, Patience K., additional, Schön, Arne, additional, Kisalu, Neville K., additional, Vistein, Rachel, additional, Dillon, Marlon, additional, Bonilla, Brian G., additional, Molina-Cruz, Alvaro, additional, Barillas-Mury, Carolina, additional, Tan, Joshua, additional, Idris, Azza H., additional, Francica, Joseph R., additional, and Seder, Robert A., additional

Published
2021
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37. A Potent Anti-Malarial Human Monoclonal Antibody Targets Circumsporozoite Protein Minor Repeats and Neutralizes Sporozoites in the Liver

Author

Wang, Lawrence T., Pereira, Lais S., Flores-Garcia, Yevel, O’Connor, James, Flynn, Barbara J., Schön, Arne, Hurlburt, Nicholas K., Dillon, Marlon, Yang, Annie S.P., Fabra-García, Amanda, Idris, Azza H., Mayer, Bryan T., Gerber, Monica W., Gottardo, Raphael, Mason, Rosemarie D., Cavett, Nicole, Ballard, Reid B., Kisalu, Neville K., Molina-Cruz, Alvaro, Nelson, Jorgen, Vistein, Rachel, Barillas-Mury, Carolina, Amino, Rogerio, Baker, David, King, Neil P., Sauerwein, Robert W., Pancera, Marie, Cockburn, Ian A., Zavala, Fidel, Francica, Joseph R., and Seder, Robert A.

Published
2020
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39. Use of a Drosophila model to identify genes regulating plasmodium growth in the mosquito

Author

Brandt, Stephanie M., Jaramillo-Gutierrez, Giovanna, Kumar, Sanjeev, Barillas-Mury, Carolina, and Schneider, David S.

Subjects
Drosophila -- Genetic aspects, Mosquitoes -- Genetic aspects, Plasmodium -- Growth, Plasmodium -- Genetic aspects, Genetic regulation -- Models, Gene expression -- Models, Company growth, Biological sciences
Abstract

We performed a forward genetic screen, using Drosophila as a surrogate mosquito, to identify host factors required for the growth of the avian malaria parasite, Plasmodium gallinaceum. We identified 18 presumed loss-of-function mutants that reduced the growth of the parasite in flies. Presumptive mutation sites were identified in 14 of the mutants on the basis of the insertion site of a transposable element. None of the identified genes have been previously implicated in innate immune responses or interactions with Plasmodium. The functions of five Anopheles gambiae homologs were tested by using RNAi to knock down gene function followed by measuring the growth of the rodent parasite, Plasmodium berghei. Loss of function of four of these genes in the mosquito affected Plasmodium growth, suggesting that Drosophila can be used effectively as a surrogate mosquito to identify relevant host factors in the mosquito.

Published
2008

40. BCG vaccine-induced protection from COVID-19 infection, wishful thinking or a game changer?

Author

Escobar, Luis E, Molina-Cruz, Alvaro, and Barillas-Mury, Carolina

Subjects
Article
Abstract

A series of epidemiological explorations have suggested a negative association between national BCG vaccination policy and the prevalence and mortality of COVID-19. Nevertheless, these comparisons are difficult to validate due to broad differences between countries such as socioeconomic status, demographic structure, rural vs. urban settings, time of arrival of the pandemic, number of diagnostic tests and criteria for testing, and national control strategies to limit the spread of COVID-19. We review evidence for the potential biological basis of BCG cross-protection from severe COVID-19 and refine the epidemiological analysis to mitigate effects of potentially confounding factors (e.g., stage of the COVID-19 epidemic, development, rurality, population density and age structure). Results fail to confirm the null hypothesis of no-association between BCG vaccination and COVID-19 mortality, and suggest that BCG could have a protective effect. Nevertheless, the analyses are restricted to coarse-scale signals and should be considered with caution. BCG vaccination clinical trials are required to corroborate the patterns detected here and to establish causality between BCG vaccination and protection from severe COVID-19. Public health implications of a plausible BCG cross-protection from severe COVID-19 are discussed.

Published
2020

41. A role for insect galectins in parasite survival

Author

Kamhawi, Shaden, Ramalho-Ortigao, Marcelo, Pham, Van M., Kumar, Sanjeev, Lawyer, Philip G., Turco, Salvatore J., Barillas-Mury, Carolina, Sacks, David L., and Valenzuela, Jesus G.

Subjects
Parasites -- Research, Parasitic insects -- Research, Biological sciences
Abstract

The exploitation of insect galectins, which are associated with embryonic developments by parasites for survival in their insect hosts, is shown. PpGalec, a tandem repeat galectin expressed in the midgut of the sand fly Phlebotomus papatasi, is used by Leishmania major as a receptor for mediating specific binding to the insect midgut, an event crucial for parasite survival and accounts for species-specific vector competence.

Published
2004

42. 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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48. Plasmodium berghei P47 is essential for ookinete protection from the Anopheles gambiae complement-like response

Author

Ukegbu, Chiamaka Valerie, Giorgalli, Maria, Yassine, Hassan, Ramirez, Jose Luis, Taxiarchi, Chrysanthi, Barillas-Mury, Carolina, Christophides, George K., and Vlachou, Dina

Subjects
Plasmodium berghei, Science, fungi, Oocysts, Protozoan Proteins, Gene Expression, Complement System Proteins, Article, Host-Parasite Interactions, Malaria, Anopheles, parasitic diseases, Animals, Medicine, Female, Gene Silencing, Sequence Deletion
Abstract

Malaria is a mosquito-borne disease affecting millions of people every year. The rodent parasite Plasmodium berghei has served as a model for human malaria transmission studies and played a pivotal role in dissecting the mosquito immune response against infection. The 6-cysteine protein P47, known to be important for P. berghei female gamete fertility, is shown to serve a different function in Plasmodium falciparum, protecting ookinetes from the mosquito immune response. Here, we investigate the function of P. berghei P47 in Anopheles gambiae mosquito infections. We show that P47 is expressed on the surface of both female gametocytes and ookinetes where it serves distinct functions in promoting gametocyte-to-ookinete development and protecting ookinetes from the mosquito complement-like response, respectively. The latter function is essential, as ookinetes lacking P47 are targeted for killing while traversing the mosquito midgut cells and eliminated upon exposure to hemolymph proteins of the complement-like system. Silencing key factors of the complement-like system restores oocyst development and disease transmission to rodent hosts. Our data establish a dual role of P. berghei P47 in vivo and reinforce the use of this parasite to study the impact of the mosquito immune response on human malaria transmission.

Published
2017

49. Mosquito cellular immunity at single-cell resolution

Author

Raddi, Gianmarco, Barletta, Ana Beatriz F., Efremova, Mirjana, Ramirez, Jose Luis, Cantera, Rafael, Teichmann, Sarah A., Barillas-Mury, Carolina, Billker, Oliver, Raddi, Gianmarco, Barletta, Ana Beatriz F., Efremova, Mirjana, Ramirez, Jose Luis, Cantera, Rafael, Teichmann, Sarah A., Barillas-Mury, Carolina, and Billker, Oliver

Abstract

Hemocytes limit the capacity of mosquitoes to transmit human pathogens. Here we profile the transcriptomes of 8506 hemocytes of Anopheles gambiae and Aedes aegypti mosquito vectors. Our data reveal the functional diversity of hemocytes, with different subtypes of granulocytes expressing distinct and evolutionarily conserved subsets of effector genes. A previously unidentified cell type in An. gambiae, which we term "megacyte," is defined by a specific transmembrane protein marker (TM7318) and high expression of lipopolysaccharide-induced tumor necrosis factor-a transcription factor 3 (LL3). Knockdown experiments indicate that LL3 mediates hemocyte differentiation during immune priming. We identify and validate two main hemocyte lineages and find evidence of proliferating granulocyte populations. This atlas of medically relevant invertebrate immune cells at single-cell resolution identifies cellular events that underpin mosquito immunity to malaria infection.

Published
2020
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