Antibody Recognition Of Plasmodium Falciparum Infected Red Blood Cells By Symptomatic And Asymptomatic Individuals In The Brazilian Amazon

In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms.1095598607Albrecht, L., Castiñeiras, C., Carvalho, B.O., Ladeia-Andrade, S., da Silva, N.S., Hoffmann, E.H.E., dalla Martha, R.C., Wunderlich, G., The South American Plasmodium falciparum var gene repertoire is limited, highly shared and possibly lacks several antigenic types (2010) Gene, 453, pp. 37-44Albrecht, L., Merino, E.F., Hoffmann, E.H.E., Ferreira, M.U., Ferreira, R.G.M., Osakabe, A.L., dalla Martha, R.C., Wunderlich, G., Extense variant gene family repertoire overlap in western Amazon Plasmodium falciparum isolates (2006) Mol Biochem Parasitol, 150, pp. 157-165Altschul, S.F., Madden, T.L., Schäffer, A.A., Zhang, J., Zhang, Z., Miller, W., Lipman, D.J., Gapped BLAST and PSI-BLAST: A new generation of protein database search programs (1997) Nucleic Acids Res, 25, pp. 3389-3402Alves, F.P., Durlacher, R.R., Menezes, M.J., Krieger, H., Silva, L.H., Camargo, E.P., High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in native Amazonian populations (2002) Am J Trop Med Hyg, 66, pp. 641-648Anderson, T.J., Su, X.Z., Bockarie, M., Lagog, M., Day, K.P., Twelve microsatellite markers for characterization of Plasmodium falciparum from finger-prick blood samples (1999) Parasitology, 119, pp. 113-125Andrews, K.T., Adams, Y., Viebig, N.K., Lanzer, M., Schwartz-Albiez, R., Adherence of Plasmodium falciparum infected erythrocytes to CHO-745 cells and inhibition of binding by protein A in the presence of human serum (2005) Int J Parasitol, 35, pp. 1127-1134Avril, M., Tripathi, A.K., Brazier, A.J., Andisi, C., Janes, J.H., Soma, V.L., Sullivan, D.J., Smith, J.D., A restricted subset of var genes mediates adherence of Plasmodium falciparum-infected erythrocytes to brain endothelial cells (2012) Proc Natl Acad Sci USA, 109, pp. 1782-1790Baruch, D.I., Pasloske, B.L., Singh, H.B., Bi, X., Ma, X.C., Feldman, M., Taraschi, T.F., Howard, R.J., Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes (1995) Cell, 82, pp. 77-87Bengtsson, A., Joergensen, L., Rask, T.S., Olsen, R.W., Andersen, M.A., Turner, L., Theander, T.G., Jensen, A.T.R., A novel domain cassette identifies Plasmodium falciparum PfEMP1 proteins binding ICAM-1 and is a target of cross-reactive, adhesion-inhibitory antibodies (2013) J Immunol, 190, pp. 240-249Bull, P.C., Berriman, M., Kyes, S., Quail, M.A., Hall, N., Kortok, M.M., Marsh, K., Newbold, C.I., Plasmodium falciparum variant surface antigen expression patterns during malaria (2005) PLoS Pathog, 1, pp. e26Bull, P.C., Kyes, S., Buckee, C.O., Montgomery, J., Kortok, M.M., Newbold, C.I., Marsh, K., An approach to classifying sequence tags sampled from Plasmodium falciparum var genes (2007) Mol Biochem Parasitol, 154, pp. 98-102Bull, P.C., Lowe, B.S., Kortok, M., Molyneux, C.S., Newbold, C.I., Marsh, K., Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria (1998) Nat Med, 4, pp. 358-360Chan, J.-A., Howell, K.B., Reiling, L., Ataide, R., Mackintosh, C.L., Fowkes, F.J.I., Petter, M., Beeson, J.G., Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity (2012) J Clin Invest, 122, pp. 3227-3238Claessens, A., Adams, Y., Ghumra, A., Lindergard, G., Buchan, C.C., Andisi, C., Bull, P.C., Rowe, J.A., A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells (2012) Proc Natl Acad Sci USA, 109, pp. 1772-1781Crompton, P.D., Kayala, M.A., Traore, B., Kayentao, K., Ongoiba, A., Weiss, G.E., Molina, D.M., Pierce, S.K., A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray (2010) Proc Natl Acad Sci USA, 107, pp. 6958-6963Freitas-Júnior, L.H., Bottius, E., Pirrit, L.A., Deitsch, K.W., Scheidig, C., Guinet, F., Nehrbass, U., Scherf, A., Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum (2000) Nature, 407, pp. 1018-1022Golnitz, U., Albrecht, L., Wunderlich, G., Var transcription profiling of Plasmodium falciparum 3D7: Assignment of cytoadherent phenotypes to dominant transcripts (2008) Malar J, 7, p. 14Guizetti, J., Scherf, A., Silence, activate, poise and switch! Mechanisms of antigenic variation in Plasmodium falciparum (2013) Cell Microbiol, 15, pp. 718-726Hasler, T., Albrecht, G.R., van Schravendijk, M.R., Aguiar, J.C., Morehead, K.E., Pasloske, B.L., Ma, C., Howard, R.J., An improved microassay for Plasmodium falciparum cytoadherence using stable transformants of Chinese hamster ovary cells expressing CD36 or intercellular adhesion molecule-1 (1993) Am J Trop Med Hyg, 48, pp. 332-347Hviid, L., Naturally acquired immunity to Plasmodium falcipa-rum malaria in Africa (2005) Acta Trop, 95, pp. 270-275Joergensen, L., Bengtsson, D.C., Bengtsson, A., Ronander, E., Berger, S.S., Turner, L., Dalgaard, M.B., Jensen, A.T.R., Surface co-expression of two different PfEMP1 antigens on single Plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1 (2010) PLoS Pathog, 6, pp. e1001083Kyes, S.A., Christodoulou, Z., Raza, A., Horrocks, P., Pinches, R., Rowe, J.A., Newbold, C.I., A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern (2003) Mol Microbiol, 48, pp. 1339-1348Lavstsen, T., Magistrado, P., Hermsen, C.C., Salanti, A., Jensen, A.T.R., Sauerwein, R., Hviid, L., Staalsoe, T., Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans (2005) Malar J 4, p. 21Lavstsen, T., Salanti, A., Jensen, A.T.R., Arnot, D.E., Theander, T.G., Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions (2003) Malar J, 2, p. 27Lavstsen, T., Turner, L., Saguti, F., Magistrado, P., Rask, T.S., Jespersen, J.S., Wang, C.W., Theander, T.G., PNAS Plus: Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children (2012) Proc Natl Acad Sci USA, 109, pp. e1791-1800Leech, J.H., Barnwell, J.W., Miller, L.H., Howard, R.J., Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes (1984) J Exp Med, 159, pp. 1567-1575Lelievre, J., Berry, A., Benoit-Vical, F., An alternative method for Plasmodium culture synchronization (2005) Exp Parasitol, 109, pp. 195-197Maier, A.G., Rug, M., O'Neill, M.T., Beeson, J.G., Marti, M., Reeder, J., Cowman, A.F., Skeleton-binding protein 1 functions at the parasitophorous vacuole membrane to traffic PfEMP1 to the Plasmodium falciparum-infected erythrocyte surface (2007) Blood, 109, pp. 1289-1297Marsh, K., Kinyanjui, S., Immune effector mechanisms in malaria (2006) Parasite Immunol, 28, pp. 51-60Medeiros, M.M., Fotoran, W.L., dalla Martha, R.C., Katsuragawa, T.H., da Silva, L.H.P., Wunderlich, G., Natural antibody response to Plasmodium falciparum merozoite antigens MSP5, MSP9 and EBA175 is associated to clinical protection in the Brazilian Amazon (2013) BMC Infect Dis, 13, p. 608Moll, K., Ljungström, I., Perlmann, H., Scherf, A., Wahlgren, M., (2008) Methods In Malaria Research, p. 330. , 5th ed., MR4/ATCC, Manassas/BioMalPar, ParisOchola, L.B., Siddondo, B.R., Ocholla, H., Nkya, S., Kimani, E.N., Williams, T.N., Makale, J.O., Craig, A.G., Specific receptor usage in Plasmodium falciparum cytoadherence is associated with disease outcome (2011) PLoS ONE, 6, pp. e14741Oleinikov, A.V., Amos, E., Frye, I.T., Rossnagle, E., Mutabingwa, T.K., Fried, M., Duffy, P.E., High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies (2009) PLoS Pathog, 5, pp. e1000386Oliveira-Ferreira, J., Lacerda, M.V., Brasil, P., Ladislau, J.L., Tauil, P.L., Daniel-Ribeiro, C.T., Malaria in Brazil: An overview (2010) Malar J, 9, p. 115Pasternak, N.D., Dzikowski, R., PfEMP1: An antigen that plays a key role in the pathogenicity and immune evasion of the malaria parasite Plasmodium falciparum (2009) Int J Biochem Cell Biol, 41, pp. 1463-1466Portugal, S., Pierce, S.K., Crompton, P.D., Young lives lost as B cells falter: What we are learning about antibody responses in malaria (2013) J Immunol, 190, pp. 3039-3046Rask, T.S., Hansen, D.A., Theander, T.G., Pedersen, A.G., Lavstsen, T., Plasmodium falciparum erythrocyte membrane protein 1 diversity in seven genomes-divide and conquer (2010) PLoS Comput Biol, 6, pp. e1000933Salanti, A., Staalsoe, T., Lavstsen, T., Jensen, A.T.R., Sowa, M.P.K., Arnot, D.E., Hviid, L., Theander, T.G., Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria (2003) Mol Microbiol, 49, pp. 179-191Scherf, A., Hernandez-Rivas, R., Buffet, P., Bottius, E., Benatar, C., Pouvelle, B., Gysin, J., Lanzer, M., Antigenic variation in malaria: In situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum (1998) EMBO J, 17, pp. 5418-5426Segurado, A.A., di Santi, S.M., Shiroma, M., In vivo and in vitro Plasmodium falciparum resistance to chloroquine, amodiaquine and quinine in the Brazilian Amazon (1997) Rev Inst Med Trop Sao Paulo, 39, pp. 85-90Su, X.Z., Heatwole, V.M., Wertheimer, S.P., Guinet, F., Herrfeldt, J.A., Peterson, D.S., Ravetch, J.A., Wellems, T.E., The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes (1995) Cell, 82, pp. 89-100Trager, W., Jensen, J.B., Human malaria parasites in continuous culture (1976) Science, 193, pp. 673-675Turner, G.D., Morrison, H., Jones, M., Davis, T.M., Looareesuwan, S., Buley, I.D., Gatter, K.C., Nagachinta, B., An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration (1994) Am J Pathol, 145, pp. 1057-1069Turner, L., Lavstsen, T., Berger, S.S., Wang, C.W., Petersen, J.E.V., Avril, M., Brazier, A.J., Theander, T.G., Severe malaria is associated with parasite binding to endothelial protein C receptor (2013) Nature, 498, pp. 502-505Tutterrow, Y.L., Avril, M., Singh, K., Long, C.A., Leke, R.J., Sama, G., Salanti, A., Taylor, D.W., High levels of antibodies to multiple domains and strains of VAR2CSA correlate with the absence of placental malaria in Cameroonian women living in an area of high Plasmodium falciparum transmission (2012) Infect Immun, 80, pp. 1479-1490Vaughan, A.M., Kappe, S.H.I., Malaria vaccine development: Persistent challenges (2012) Curr Opin Immunol, 24, pp. 324-331Voss, T.S., Healer, J., Marty, A.J., Duffy, M.F., Thompson, J.K., Beeson, J.G., Reeder, J.C., Cowman, A.F., A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria (2006) Nature, 439, pp. 1004-1008Walliker, D., Quakyi, I.A., Wellems, T.E., McCutchan, T.F., Szarfman, A., London, W.T., Corcoran, L.M., Carter, R., Genetic analysis of the human malaria parasite Plasmodium falciparum (1987) Science, 236, pp. 1661-1666Warimwe, G.M., Keane, T.M., Fegan, G., Musyoki, J.N., Newton, C.R.J.C., Pain, A., Berriman, M., Bull, P.C., Plasmodium falciparum var gene expression is modified by host immunity (2009) Proc Natl Acad Sci USA, 106, pp. 21801-21806Weiss, G.E., Traore, B., Kayentao, K., Ongoiba, A., Doumbo, S., Doumtabe, D., Kone, Y., Crompton, P.D., The Plasmodium falciparum-specific human memory B cell compartment expands gradually with repeated malaria infections (2010) PLoS Pathog, 6, pp. e1000912(2011), www.who.int/malaria/world_malaria_report_2011/en/, WHO-World Health Organization, World malaria report 2011. Available from(2013), www.who.int/malaria/publications/world_malaria_report_2013/en/, WHO-World Health Organization, World Malaria Report 2013. Available fro

Modulation of parasitemia and antibody responce to Trypanosoma cruzy by cyclophosphamide in Calomys callosus (Rodentia, Cricetidae) Modulação da parasitemia e da resposta de anticorpos ao Trypanosoma cruzi pela ciclofosfamida em Calomys callosus (Rodentia, Cricetidae)

Calomys callosus a wild rodent, previously described as harboring Trypanosoma cruzi, has a low susceptibility to infection by this protozoan. Experiments were designed to evaluate the contribution of the immune response to the resistance to T. cruzi infection exhibited by C. calossus. Animals were submitted to injections of high (200 mg/kg body weight) and low (20 mg/kg body weight) doses of cyclophosphamide on days -1 or -1 and +5, and inoculated with 4 x 10³ T. cruzi on day O. Parasitemia, mortality and antibody response as measured by direct agglutination of trypomastigotes were observed. Two hundred mg doses of cyclophosphamide resulted in higher parasitemia and mortality as well as in suppression of the antibody response. A single dose of 20 mg enhanced antibody levels on the 20th day after infection, while an additional dose did not further increase antibody production. Parasitemia levels were not depressed, but rather increased in both these groups as compared to untreated controls. Passive transfer of hyperimmune C. callosus anti-T. cruzi serum to cyclophosphamide immunosuppressed animals resulted in lower parasitemia and mortality rates. These results indicate that the immune response plays an important role in the resistance of C. callossus to T. cruzi.<br>Calomys-callosus, roedor silvestre, que já foi encontrado naturalmente infectado pelo Trypanosoma cruzi, tem baixa suscetibilidade à infecção experimental por este protozoário. Foram feitos experimentos para avaliar a contribuição da resposta imune a essa baixa suscetibilidade. Animais foram submetidos a injeção de doses altas (200 mg/kg peso corporal) ou doses baixas (20 mg/kg peso corporal) de ciclofosfamida nos dias -1 ou -1 e +5, e inoculados com 4 x 10³ T. cruzi no dia O. Observou-se a curva de parasitemia, mortalidade e resposta de anticorpos medida por aglutinação direta de tripomastigotas. Doses de 200 mg resultaram em parasitemia e mortalidade mais elevada e supressão da resposta de anticorpos. Uma dose de 20 mg aumentou os níveis de anticorpos no 20º dia após a infecção, enquanto a administração de uma segunda dose não alterou significativamente a produção de anticorpos. Os níveis de parasitemia não diminuíram, mas pelo contrário, elevaram-se em relação aos animais testemunhos, em ambos os grupos. A transferência passiva de soro anti-T. cruzi de C. callosus resultou em parasitemia e mortalidade mais baixa nos animais imunossuprimidos. Estes resultados indicam que a resposta imune é um importante fator na resistência de C. callosus à infecção por T. cruzi

Planting density and initial growth of two tree species adapted to the semi-arid region

Planting densities influence several aspects of forest formation, including management practices, timber yield, quality, and extraction, and consequently its production costs. The objective of this study was to evaluate Mimosa caesalpiinifolia and Gliricidia sepium growth as a function of planting density (400, 600, 800, 1000, and 1200 plants ha-1) and plant age. The species were evaluated every 90 days for plant height (PH), crown diameter (CD) and root collar diameter (RCD) (10 cm above the ground), with the first evaluation performed at 90 days and the last at 720 days. When plants were one year of age and beyond, evaluations were conducted also for stem diameter at breast height (DBH) (1.30 m above the ground). A randomized block design with split-plots and three replicates was adopted. Species were assigned to plots, planting densities were assigned to subplots, and evaluation ages were assigned to subsubplots. The four traits in both species had their values decreased as planting density increased, but continually increased as plant age increased. For PH and RCD there was an alternation between species superiority, with gliricidia being superior to sabiá at some ages, while the opposite occurred at other ages. As to CD the species only differed in the last measurement, gliricidia being superior. With regard to DBH, gliricidia was superior starting from the second measurement. There was an effect of the species × ages interaction for the four traits and also an effect of the densities × ages interaction for CD and DBH