scholarly journals Proteomic Analysis ofPlasmodiumMerosomes: The Link Between Liver and Blood Stages in Malaria

2019 ◽  
Author(s):  
Melanie J Shears ◽  
Raja Sekhar Nirujogi ◽  
Kristian E Swearingen ◽  
Santosh Renuse ◽  
Satish Mishra ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Life Cycle Stage ◽  
Blood Stage ◽  
Quantitative Detection ◽  
List Type ◽  
Liver Stage ◽  
Core Set ◽  
Blood Stage Infection ◽  
Malaria Model ◽  
Stage Infection

SummaryThe pre-erythrocytic liver stage of the malaria parasite, comprising sporozoites and the liver stages into which they develop, remains one of the least understood parts of the lifecycle, in part owing to the low numbers of parasites. Nonetheless, it is recognized as an important target for anti-malarial drugs and vaccines. Here we provide the first proteomic analysis of merosomes, which define the final phase of the liver stage and are responsible for initiating the blood stage of infection. We identify a total of 1879 parasite proteins, and a core set of 1188 proteins quantitatively detected in every biological replicate, providing an extensive picture of the protein repertoire of this stage. This unique dataset will allow us to explore key questions about the biology of merosomes and hepatic merozoites.HighlightsFirst proteome of the merosome stage of malaria parasitesQuantitative detection of 1188 parasite proteins across 3 biological replicatesComparison to blood stage proteomes identifies shared and unique proteinsDiscovery of cleaved PEXEL motifs highlights liver stage protein exportIn BriefThe merosome stage that links malaria liver and blood stage infection is poorly understood. Here we provide the first proteome of this life cycle stage using thePlasmodium bergheirodent malaria model.Graphical Abstract

scholarly journals A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

iScience ◽  
2020 ◽  
Vol 23 (8) ◽  
pp. 101381
Author(s):  
Carola Schäfer ◽  
Wanlapa Roobsoong ◽  
Niwat Kangwanrangsan ◽  
Martino Bardelli ◽  
Thomas A. Rawlinson ◽  
...  
Keyword(s):  
Mouse Model ◽  
Plasmodium Vivax ◽  
Blood Stage ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Liver Stage ◽  
Blood Stage Infection ◽  
Stage Transition ◽  
Stage Infection

scholarly journals Malaria Blood Stage Suppression of Liver Stage Immunity by Dendritic Cells

2003 ◽  
Vol 197 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Carlos Ocaña-Morgner ◽  
Maria M. Mota ◽  
Ana Rodriguez
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Blood Stage ◽  
Liver Stage ◽  
Cell Responses ◽  
Blood Stage Infection ◽  
Stage Infection

Malaria starts with Plasmodium sporozoites infection of the host's liver, where development into blood stage parasites occurs. It is not clear why natural infections do not induce protection against the initial liver stage and generate low CD8+ T cell responses. Using a rodent malaria model, we show that Plasmodium blood stage infection suppresses CD8+ T cell immune responses that were induced against the initial liver stage. Blood stage Plasmodium affects dendritic cell (DC) functions, inhibiting maturation and the capacity to initiate immune responses and inverting the interleukin (IL)-12/IL-10 secretion pattern. The interaction of blood stage parasites with DCs induces the secretion of soluble factors that inhibit the activation of CD8+ T cells in vitro and the suppression of protective CD8+ T cell responses against the liver stage in vivo. We propose that blood stage infection induces DCs to suppress CD8+ T cell responses in natural malaria infections. This evasion mechanism leaves the host unprotected against reinfection by inhibiting the immune response against the initial liver stage of the disease.

scholarly journals Resolving the cause of recurrent Plasmodium vivax malaria probabilistically

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aimee R. Taylor ◽  
James A. Watson ◽  
Cindy S. Chu ◽  
Kanokpich Puaprasert ◽  
Jureeporn Duanguppama ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Blood Stage ◽  
High Dose ◽  
Time To Event ◽  
Liver Stage ◽  
Plasmodium Vivax Malaria ◽  
Blood Stage Infection ◽  
Stage Infection

AbstractRelapses arising from dormant liver-stage Plasmodium vivax parasites (hypnozoites) are a major cause of vivax malaria. However, in endemic areas, a recurrent blood-stage infection following treatment can be hypnozoite-derived (relapse), a blood-stage treatment failure (recrudescence), or a newly acquired infection (reinfection). Each of these requires a different prevention strategy, but it was not previously possible to distinguish between them reliably. We show that individual vivax malaria recurrences can be characterised probabilistically by combined modelling of time-to-event and genetic data within a framework incorporating identity-by-descent. Analysis of pooled patient data on 1441 recurrent P. vivax infections in 1299 patients on the Thailand–Myanmar border observed over 1000 patient follow-up years shows that, without primaquine radical curative treatment, 3 in 4 patients relapse. In contrast, after supervised high-dose primaquine only 1 in 40 relapse. In this region of frequent relapsing P. vivax, failure rates after supervised high-dose primaquine are significantly lower (∼3%) than estimated previously.

scholarly journals A Plasmodium berghei putative serine-threonine kinase 2 (PBANKA_0311400) is required for late liver stage development and timely initiation of blood stage infection

Biology Open ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. bio042028
Author(s):  
Ravi Jillapalli ◽  
Sunil Kumar Narwal ◽  
Surendra Kumar Kolli ◽  
Babu S. Mastan ◽  
Rameswara Reddy Segireddy ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Blood Stage ◽  
Serine Threonine Kinase ◽  
Timely Initiation ◽  
Liver Stage ◽  
Threonine Kinase ◽  
Blood Stage Infection ◽  
Stage Development ◽  
Stage Infection

Plasmodium vivax Latent Liver Stage Infection and Relapse: Biological Insights and New Experimental Tools

2021 ◽  
Vol 75 (1) ◽  
Author(s):  
Carola Schäfer ◽  
Gigliola Zanghi ◽  
Ashley M. Vaughan ◽  
Stefan H.I. Kappe
Keyword(s):  
Plasmodium Vivax ◽  
Blood Stage ◽  
Annual Review ◽  
Publication Date ◽  
Liver Stage ◽  
Human Malaria Parasite ◽  
Treatment And Prevention ◽  
Parasite Stage ◽  
Blood Stage Infection ◽  
Stage Infection

Plasmodium vivax is the most widespread human malaria parasite, in part because it can form latent liver stages known as hypnozoites after transmission by female anopheline mosquitoes to human hosts. These persistent stages can activate weeks, months, or even years after the primary clinical infection; replicate; and initiate relapses of blood stage infection, which causes disease and recurring transmission. Eliminating hypnozoites is a substantial obstacle for malaria treatment and eradication since the hypnozoite reservoir is undetectable and unaffected by most antimalarial drugs. Importantly, in some parts of the globe where P. vivax malaria is endemic, as many as 90% of P. vivax blood stage infections are thought to be relapses rather than primary infections, rendering the hypnozoite a major driver of P. vivax epidemiology. Here, we review the biology of the hypnozoite and recent discoveries concerning this enigmatic parasite stage. We discuss treatment and prevention challenges, novel animal models to study hypnozoites and relapse, and hypotheses related to hypnozoite formation and activation. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Plasmodium yoelii Sporozoites with Simultaneous Deletion of P52 and P36 Are Completely Attenuated and Confer Sterile Immunity against Infection

2007 ◽  
Vol 75 (8) ◽  
pp. 3758-3768 ◽  
Author(s):  
Mehdi Labaied ◽  
Anke Harupa ◽  
Ronald F. Dumpit ◽  
Isabelle Coppens ◽  
Sebastian A. Mikolajczak ◽  
...  
Keyword(s):  
Host Cell ◽  
Genetic Manipulation ◽  
Parasitophorous Vacuole ◽  
Plasmodium Yoelii ◽  
Blood Stage ◽  
Mammalian Host ◽  
Electron Microscopic ◽  
Rodent Host ◽  
Blood Stage Infection ◽  
Stage Infection

ABSTRACT Malaria infection starts when sporozoites are transmitted to the mammalian host during a mosquito bite. Sporozoites enter the blood circulation, reach the liver, and infect hepatocytes. The formation of a parasitophorous vacuole (PV) establishes their intracellular niche. Recently, two members of the 6-Cys domain protein family, P52 and P36, were each shown to play an important albeit nonessential role in Plasmodium berghei sporozoite infectivity for the rodent host. Here, we generated p52/p36-deficient Plasmodium yoelii parasites by the simultaneous deletion of both genes using a single genetic manipulation. p52/p36-deficient parasites exhibited normal progression through the life cycle during blood-stage infection, transmission to mosquitoes, mosquito-stage development, and sporozoite infection of the salivary glands. p52/p36-deficient sporozoites also showed normal motility and cell traversal activity. However, immunofluorescence analysis and electron microscopic observations revealed that p52/p36-deficient parasites did not form a PV within hepatocytes in vitro and in vivo. The p52/p36-deficient parasites localized as free entities in the host cell cytoplasm or the host cell nucleoplasm and did not develop as liver stages. Consequently, they did not cause blood-stage infections even at high sporozoite inoculation doses. Mice immunized with p52/p36-deficient sporozoites were completely protected against infectious sporozoite challenge. Our results demonstrate for the first time the generation of two-locus gene deletion-attenuated parasites that infect the liver but do not progress to blood-stage infection. The study will critically guide the design of Plasmodium falciparum live attenuated malaria vaccines.

The Plasmodium falciparum var gene transcription strategy at the onset of blood stage infection in a human volunteer

2009 ◽  
Vol 58 (4) ◽  
pp. 478-480 ◽  
Author(s):  
Christian W. Wang ◽  
Cornelus C. Hermsen ◽  
Robert W. Sauerwein ◽  
David E. Arnot ◽  
Thor G. Theander ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Gene Transcription ◽  
Blood Stage ◽  
Human Volunteer ◽  
Blood Stage Infection ◽  
Stage Infection ◽  
Var Gene

Merozoite vaccination of rhesus monkeys against plasmodium knowlesi malaria; immunity to sporozoite (mosquito-transmitted) challenge

Parasitology ◽  
1977 ◽  
Vol 74 (2) ◽  
pp. 191-198 ◽  
Author(s):  
W. H. G. Richards ◽  
G. H. Mitchell ◽  
G. A. Butcher ◽  
S. Cohen
Keyword(s):  
Rhesus Monkeys ◽  
Malaria Vaccine ◽  
Plasmodium Knowlesi ◽  
Blood Stage ◽  
Parasite Development ◽  
Post Vaccination ◽  
Challenge Strain ◽  
Freeze Dried ◽  
Blood Stage Infection ◽  
Stage Infection

Five normal rhesus monkeys were infected with Plasmodium knowlesi sporozoites (A-strain); two developed rapidly fatal malaria and three chrinic relapsing infections. Vaccination with P. knowlesi (W-strain) merozoites (unmodified or formol-treated and freeze-dried) in Freund's complete adjuvant (FCA) did not inhibit pre-erythrocytic parasite development after challenge with A-strain sporozoites. However, the subsequent blood-stage infection was terminated in nine out of ten vaccinated monkeys even though the challenge strain was different form that used for vaccination. The degree of parasitaemia (0·01–0·70 %) and brevity of infection (1–12 days) in six animals vaccinated with untreated merzoites was similar to that observed after direct challenge with blood-stage parasites. Monkeys were equally resistant to sporozoite challenge given as the post-vaccination infection or administered 6 months after blood challenge. These results are discussed in relation to the development of a human malaria vaccine.

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