Host-Parasite Interaction: Selective Pv-fam-a Family Proteins of<i>Plasmodium vivax</i>Bind to a Restricted Number of Human Erythrocyte Receptors

Zeeshan, Mohammad; Tyagi, Rupesh Kumar; Tyagi, Kriti; Alam, Mohd Shoeb; Sharma, Yagya D.

doi:10.1093/infdis/jiu558

Cited by 41 publications

(69 citation statements)

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“…These combined effects beg the question of whether the localization of other members of the PvTRAg family is also associated with CVCs. Of these five PvTRAg proteins, PvTRAg_26 and PvTRAg_29 showed binding activity to host erythrocytes in a recent study (14). However, the detailed functions of the proteins remain unknown, and further investigations are required.…”

Section: Discussionmentioning

confidence: 97%

“…Fifteen of the tryptophan-rich antigens of P. vivax (PvTRAgs) that induced significant cellular and humoral responses in humans have been immunologically characterized and have shown few genetic polymorphisms in the parasite population (11). Recently, 10 of the 36 PvTRAgs have been shown to bind to human erythrocytes (14) and might be exploited to develop therapeutic agents against vivax malaria.…”

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confidence: 99%

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Immunoprofiling of the Tryptophan-Rich Antigen Family in Plasmodium vivax

Wang

Cheng

et al. 2015

Infect Immun

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h Tryptophan-rich antigens (TRAgs) are an antigen family that has been identified in human and rodent malaria parasites. TRAgs have been proposed as candidate antigens for potential vaccines. The Plasmodium vivax TRAg (PvTRAg) family includes 36 members. Each PvTRAg contains a tryptophan-rich (TR) domain in the C-terminal region. In this study, we recombinantly expressed all 36 PvTRAgs using a cell-free expression system, and, for the first time, profiled the IgG antibody responses against all PvTRAgs in the sera from 96 vivax malaria patients and 40 healthy individuals using protein microarray technology. The mean seropositive rate for all PvTRAgs was 60.3%. Among them, nine PvTRAgs were newly identified in this study and showed a seropositive rate of >50%. Five of them, PvTRAg_13, PvTRAg_15, PvTRAg_16, PvTRAg_26, and PvTRAg_29, produced higher levels of IgG antibody, even in low-endemicity countries. In addition, the results of an immunofluorescence analysis suggest that PvTRAgs are, at least in part, associated with caveola-vesicle complexes, a unique structure of P. vivax-infected erythrocytes. The mechanism of formation and the function of these abundant membrane structures are not known. Further investigation aimed at determining the functions of these proteins would lead to a better understanding of the blood-stage biology of P. vivax.

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

Immunoprofiling of the Tryptophan-Rich Antigen Family in Plasmodium vivax

Wang

Cheng

et al. 2015

Infect Immun

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“…PCR cloning, expression, and purification of histidine-tagged recombinant proteins of 21 PvTRAgs have been described elsewhere (23). These purified recombinant proteins were quantified by BCA kit according to the manufacturer's instructions (Thermo Scientific, Rockford, IL) and used for Western blot analysis, enzyme-linked immunosorbent assay (ELISA), and peripheral blood mononuclear cell stimulation.…”

Section: Methodsmentioning

confidence: 99%

“…These PCR products were gel purified and sequenced as described elsewhere (24). The products were sequenced from both strands using nested primers described earlier (23) and an ABI BigDye terminator ready reaction kit version 3.1 on an ABI Prism 3130xl genetic analyzer (PE Applied Biosystems, Foster City, CA). The BioEdit sequence alignment editor and GeneDoc version 2.6.002 were used to analyze the sequencing electropherograms and generate sequence alignment, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Several of these proteins have shown the stage-specific expression, and some of them are expressed at merozoite stage (22). Earlier, we showed that 10 of these 36 PvTRAgs, including those expressed by the merozoites, bind to uninfected human erythrocytes that can be inhibited by the patients' sera, thereby indicating their biological role in the parasite life cycle (17,23). We also immunologically characterized 15 of these proteins and showed that P. vivax-exposed individuals produce antibodies and generate the memory T-cell responses against them (9,14,24).…”

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CD4 ⁺ T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

2015

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Tryptophan-rich proteins play important biological functions for the Plasmodium parasite. Plasmodium vivax contains remarkably large numbers of such proteins belonging to the "Pv-fam-a" family that need to be characterized. Earlier, we reported the presence of memory T cells and naturally acquired antibodies against 15 of these proteins in P. vivax malaria-exposed individuals (M. Zeeshan, H. Bora, and Y. D. Sharma, J Infect Dis 207:175-185, 2013, http://dx.doi.org/10.1093/infdis/jis650). Here, we sought to characterize and ascertain the cross talk between effector responses of T and B cells in malarial patients against all Pvfam-a family proteins. Therefore, we expressed the remaining 21 of these proteins in Escherichia coli and studied the humoral and cellular immune responses based on the same parameters used in our previous study. Naturally acquired IgG antibodies were detected against all 21 antigens in P. vivax patient sera (37.7 to 94.4% seropositivity). These antigens were able to activate the lymphocytes of P. vivax-exposed individuals, and the activated CD4 ؉ T lymphocytes produced higher levels of Th1 (interleukin-2 [IL-2] and gamma interferon [IFN-␥]) and Th2 (IL-4 and IL-10) cytokines than the healthy controls, but the response was Th2 biased. The combined results of present and previous studies seem to suggest a striking link between induction of the CD4 ؉ T cell response and naturally acquired antibodies against all 36 proteins of the Pv-fam-a family, the majority of them having conserved sequences in the parasite population. Further work is required to utilize this information to develop immunotherapeutic treatments for this disease. Despite continued efforts to control malaria, it remains a major health problem in affected tropical countries. There is an urgent need to develop an effective malaria vaccine and newer antimalarial drugs to control this disease. This requires the identification and characterization of newer parasite molecules that play significant biological function for the survival of the parasite and could generate cellular and humoral immune responses in humans to provide protection against the disease. Previous studies have shown that humoral and T-cell-mediated immune responses are induced against malaria parasite, and these responses were found to be antigen and stage specific (1). Antibodies come to play their role as soon as the parasite enters the human body. These antibodies not only clear the parasite by opsonization but also block the invasion of host cells by the parasite. Therefore, the humoral immune response plays a critical role in controlling the parasite.A role for dendritic cells, monocyte/macrophages, B cells, and several groups of T cells has been proposed in the cellular immune response against malaria (1-4). Some specific cytokines are produced from peripheral blood mononuclear cells in response to parasite infection, which further activates the host's macrophages, neutrophils, T cells, and natural killer cells to react against the parasites (5). Monocytes/ma...

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Host–parasite interaction: multiple sites in the Plasmodium vivax tryptophan‐rich antigen PvTRAg38 interact with the erythrocyte receptor band 3

et al. 2016

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Tryptophan-rich antigens of malarial parasites interact with host molecules and play an important role in parasite survival. Merozoite expressed Plasmodium vivax tryptophan-rich antigen PvTRAg38 binds to human erythrocytes and facilitates parasite growth in a heterlologous Plasmodium falciparum culture system. Recently, we identified band 3 in human erythrocytes as one of its receptors, although the receptor-ligand binding mechanisms remain unknown. In the present study, using synthetic mutated peptides of PvTRAg38, we show that multiple amino acid residues of its 12 amino acid domain (KWVQWKNDKIRS) at position 197-208 interact with three different ectodomains of band 3 receptor on human erythrocytes. Our findings may help in the design of new therapeutic approaches for malaria.

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Host-Parasite Interaction: Selective Pv-fam-a Family Proteins ofPlasmodium vivaxBind to a Restricted Number of Human Erythrocyte Receptors

Abstract: This redundancy may be useful for the parasite to invade red blood cells and cause disease pathogenesis, and it can be exploited to develop therapeutics against P. vivax malaria.

Cited by 41 publications

References 130 publications

Immunoprofiling of the Tryptophan-Rich Antigen Family in Plasmodium vivax

Immunoprofiling of the Tryptophan-Rich Antigen Family in Plasmodium vivax

CD4 ⁺ T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

Host–parasite interaction: multiple sites in the Plasmodium vivax tryptophan‐rich antigen PvTRAg38 interact with the erythrocyte receptor band 3

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Host-Parasite Interaction: Selective Pv-fam-a Family Proteins ofPlasmodium vivaxBind to a Restricted Number of Human Erythrocyte Receptors

Abstract: This redundancy may be useful for the parasite to invade red blood cells and cause disease pathogenesis, and it can be exploited to develop therapeutics against P. vivax malaria.

Cited by 41 publications

References 130 publications

Immunoprofiling of the Tryptophan-Rich Antigen Family in Plasmodium vivax

Immunoprofiling of the Tryptophan-Rich Antigen Family in Plasmodium vivax

CD4 + T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

Host–parasite interaction: multiple sites in the Plasmodium vivax tryptophan‐rich antigen PvTRAg38 interact with the erythrocyte receptor band 3

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CD4 ⁺ T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens