scholarly journals Absence of PEXEL-Dependent Protein Export in Plasmodium Liver Stages Cannot Be Restored by Gain of the HSP101 Protein Translocon ATPase

2021 ◽  
Vol 12 ◽  
Author(s):  
Oriana Kreutzfeld ◽  
Josephine Grützke ◽  
Alyssa Ingmundson ◽  
Katja Müller ◽  
Kai Matuschewski
Keyword(s):  
Plasmodium Berghei ◽  
Protein Export ◽  
Malarial Parasite ◽  
Core Complex ◽  
Liver Stage ◽  
Cell Remodeling ◽  
Dependent Protein ◽  
Transgenic Parasites ◽  
Infected Liver ◽  
Liver Infection

Host cell remodeling is critical for successful Plasmodium replication inside erythrocytes and achieved by targeted export of parasite-encoded proteins. In contrast, during liver infection the malarial parasite appears to avoid protein export, perhaps to limit exposure of parasite antigens by infected liver cells. HSP101, the force-generating ATPase of the protein translocon of exported proteins (PTEX) is the only component that is switched off during early liver infection. Here, we generated transgenic Plasmodium berghei parasite lines that restore liver stage expression of HSP101. HSP101 expression in infected hepatocytes was achieved by swapping the endogenous promoter with the ptex150 promoter and by inserting an additional copy under the control of the elongation one alpha (ef1α) promoter. Both promoters drive constitutive and, hence, also pre-erythrocytic expression. Transgenic parasites were able to complete the life cycle, but failed to export PEXEL-proteins in early liver stages. Our results suggest that PTEX-dependent early liver stage export cannot be restored by addition of HSP101, indicative of alternative export complexes or other functions of the PTEX core complex during liver infection.

scholarly journals Antigen Export during Liver Infection of the Malaria Parasite Augments Protective Immunity

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Georgina N. Montagna ◽  
Macarena Beigier-Bompadre ◽  
Martina Becker ◽  
Richard A. Kroczek ◽  
Stefan H. E. Kaufmann ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
Protective Immunity ◽  
Malaria Parasite ◽  
Protein Export ◽  
Mhc I ◽  
Liver Stage ◽  
Cell Responses ◽  
Liver Infection

ABSTRACTProtective immunity against preerythrocytic malaria parasite infection is difficult to achieve. IntracellularPlasmodiumparasites likely minimize antigen presentation by surface-expressed major histocompatibility complex class I (MHC-I) molecules on infected cells, yet they actively remodel their host cells by export of parasite factors. Whether exported liver-stage proteins constitute better candidates for MHC-I antigen presentation to CD8+T lymphocytes remains unknown. Here, we systematically characterized the contribution of protein export to the magnitude of antigen-specific T-cell responses againstPlasmodium bergheiliver-stage parasites in C57BL/6 mice. We generated transgenic sporozoites that secrete a truncated ovalbumin (OVA) surrogate antigen only in the presence of an amino-terminal protein export element. Immunization with live attenuated transgenic sporozoites revealed that antigen export was not critical for CD8+T-cell priming but enhanced CD8+T-cell proliferation in the liver. Upon transfer of antigen-specific CD8+T cells, liver-stage parasites secreting the target protein were eliminated more efficiently. We conclude thatPlasmodiumparasites strictly control protein export during liver infection to minimize immune recognition. Strategies that enhance the discharge of parasite proteins into infected hepatocytes could improve the efficacy of candidate preerythrocytic malaria vaccines.IMPORTANCEVaccine development againstPlasmodiumparasites remains a priority in malaria research. The most advanced malaria subunit vaccine candidates containPlasmodiumsurface proteins with important roles for parasite vital functions. A fundamental question is whether recognition by effector CD8+T cells is restricted to sporozoite surface antigens or extends to parasite proteins that are synthesized during the extensive parasite expansion phase in the liver. Using a surrogate model antigen, we found that a cytoplasmic antigen is able to induce robust protective CD8+T-cell responses, but protein export further enhances immunogenicity and protection. Our results show that a cytoplasmic localization does not exclude a protein’s candidacy for malaria subunit vaccines and that protein secretion can enhance protective immunity.

Contrasts in antigen expression in the erythrocytic and exoerythrocytic stages of rodent malaria

Parasitology ◽  
1989 ◽  
Vol 99 (2) ◽  
pp. 165-170 ◽  
Author(s):  
A. Suhrbier ◽  
M. F. Wiser ◽  
L. Winger ◽  
P. Harte ◽  
M. F. Newton ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Plasmodium Berghei ◽  
Antigen Expression ◽  
Liver Stage ◽  
Rodent Malaria ◽  
Antigenic Composition ◽  
Antibody Staining ◽  
Infected Liver ◽  
Two Stages ◽  
Indirect Immunofluorescent

SummaryThe time and Site of expression of five antigens, recognized by monoclonal antibodies raised against blood-stage parasites, were studied in the exoerythrocytic stage ofPlasmodium bergheiusing indirect immunofluorescent antibody staining. Two monoclonal antibodies (W 3. 5, I 2. 6), which stain the cytoplasm of infected erythrocytes, did not stain the cytoplasm of the infected liver cell but stained the parasite itself suggesting a difference in the antigenic architecture of the erythrocytic and exoerythrocytic parasites. Another antibody (17. 6. 1) revealed a further difference in the antigenic composition of the blood and liver-stage parasites being expressed almost exclusively in the former. Two others (C139 and 17. 3. 9) showed broadly similar patterns of expression in these two stages of the malarial life-cycle.

scholarly journals Role of Plasmodium berghei cGMP-dependent Protein Kinase in Late Liver Stage Development

2009 ◽  
Vol 285 (5) ◽  
pp. 3282-3288 ◽  
Author(s):  
Adebola Falae ◽  
Audrey Combe ◽  
Anburaj Amaladoss ◽  
Teresa Carvalho ◽  
Robert Menard ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Plasmodium Berghei ◽  
Dependent Protein Kinase ◽  
Liver Stage ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Stage Development

scholarly journals Association of Plasmodium berghei With the Apical Domain of Hepatocytes Is Necessary for the Parasite's Liver Stage Development

2020 ◽  
Vol 9 ◽  
Author(s):  
Lakshmi Balasubramanian ◽  
Vanessa Zuzarte-Luís ◽  
Tabish Syed ◽  
Debakshi Mullick ◽  
Saptarathi Deb ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Liver Stage ◽  
Apical Domain ◽  
Stage Development

scholarly journals High efficacy in vitro selection procedure for generating transgenic parasites of Plasmodium berghei using an antibiotic toxic to rodent hosts

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Akira Soga ◽  
Hironori Bando ◽  
Mami Ko-ketsu ◽  
Hirono Masuda-Suganuma ◽  
Shin-ichiro Kawazu ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
In Vitro Selection ◽  
Selection Procedure ◽  
High Efficacy ◽  
Transgenic Parasites

Expression profiles of peroxiredoxins in liver stage of the rodent malaria parasite Plasmodium berghei

2013 ◽  
Vol 62 (3) ◽  
pp. 337-340 ◽  
Author(s):  
Miho Usui ◽  
Hirono Masuda-Suganuma ◽  
Shinya Fukumoto ◽  
Jose Ma. M. Angeles ◽  
Noboru Inoue ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Malaria Parasite ◽  
Expression Profiles ◽  
Rodent Malaria Parasite ◽  
Liver Stage ◽  
Rodent Malaria ◽  
Parasite Plasmodium

scholarly journals Suppressor Analysis Reveals a Role for SecY in the SecA2-Dependent Protein Export Pathway of Mycobacteria

2013 ◽  
Vol 195 (19) ◽  
pp. 4456-4465 ◽  
Author(s):  
L. S. Ligon ◽  
N. W. Rigel ◽  
A. Romanchuk ◽  
C. D. Jones ◽  
M. Braunstein
Keyword(s):  
Protein Export ◽  
Export Pathway ◽  
Dependent Protein ◽  
Suppressor Analysis

scholarly journals Mice Deficient in Interleukin-4 (IL-4) or IL-4 Receptor α Have Higher Resistance to Sporozoite Infection with Plasmodium berghei (ANKA) than Do Naive Wild-Type Mice

2004 ◽  
Vol 72 (1) ◽  
pp. 322-331 ◽  
Author(s):  
Michael Saeftel ◽  
Andreas Krueger ◽  
Sandra Arriens ◽  
Volker Heussler ◽  
Paul Racz ◽  
...  
Keyword(s):  
Nk Cells ◽  
Plasmodium Berghei ◽  
Nk Cell ◽  
Interleukin 4 ◽  
Mouse Strains ◽  
No Production ◽  
Liver Stage ◽  
Innate Immune Mechanism ◽  
Ifn Γ

ABSTRACT BALB/c interleukin-4 (IL-4−/−) or IL-4 receptor-α (IL-4rα−/−) knockout (KO) mice were used to assess the roles of the IL-4 and IL-13 pathways during infections with the blood or liver stages of plasmodium in murine malaria. Intraperitoneal infection with the blood-stage erythrocytes of Plasmodium berghei (ANKA) resulted in 100% mortality within 24 days in BALB/c mice, as well as in the mutant mouse strains. However, when infected intravenously with the sporozoite liver stage, 60 to 80% of IL-4−/− and IL-4rα−/− mice survived, whereas all BALB/c mice succumbed with high parasitemia. Compared to infected BALB/c controls, the surviving KO mice showed increased NK cell numbers and expression of inducible nitric oxide synthase (iNOS) in the liver and were able to eliminate parasites early during infection. In vivo blockade of NO resulted in 100% mortality of sporozoite-infected KO mice. In vivo depletion of NK cells also resulted in 80 to 100% mortality, with a significant reduction in gamma interferon (IFN-γ) production in the liver. These results suggest that IFN-γ-producing NK cells are critical in host resistance against the sporozoite liver stage by inducing NO production, an effective killing effector molecule against Plasmodium. The absence of IL-4-mediated functions increases the protective innate immune mechanism identified above, which results in immunity against P. berghei infection in these mice, with no major role for IL-13.

In vitro Ookinete Development of the Rodent Malarial Parasite, Plasmodium berghei

1974 ◽  
Vol 60 (5) ◽  
pp. 819 ◽  
Author(s):  
Maria C. Rosales-Ronquillo ◽  
Paul H. Silverman
Keyword(s):  
Plasmodium Berghei ◽  
Malarial Parasite ◽  
Parasite Plasmodium
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