Critical Role for Heat Shock Protein 20 (HSP20) in Migration of Malarial Sporozoites

Montagna, Georgina N.; Buscaglia, Carlos A.; Münter, Sylvia; Goosmann, Christian; Frischknecht, Friedrich; Brinkmann, Volker; Matuschewski, Kai

doi:10.1074/jbc.m111.302109

Cited by 60 publications

(77 citation statements)

References 76 publications

(82 reference statements)

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“…Bypassing intradermal migration by intravenous syringe inoculation resulted in high parasite burden in the liver. This finding using two developmental stages of sporozoites provides independent support for our previous experimental genetics evidence that fast and continuous gliding locomotion is only important for intradermal migration and not for hepatocyte invasion in vitro and in vivo (32). In hsp20(Ϫ) sporozoites, speed and cellular adhesion is dramatically altered, resulting in impaired natural malaria transmission but perfectly normal host cell invasion (32,50).…”

Section: Discussionsupporting

confidence: 68%

“…This delivery route previously revealed locomotion defects in a mutant parasite line, leading to the conclusion that fast and continuous gliding locomotion is only required for intradermal migration of Plasmodium sporozoites (32). In good agreement with a reduced proportion of gliding sporozoites and cell traversal, parasite loads in the liver were significantly (P Ͻ 0.05) reduced in hemocoel sporozoite-infected compared to sali- vary gland-infected mice (Fig.…”

Section: Hemocoel Sporozoites Perform Continuous Gliding Locomotionsupporting

confidence: 65%

“…Previous work established that fast gliding locomotion is only required for intradermal migration and not a prerequisite for liver infectivity (32). To corroborate these findings, we first infected cultured hepatoma cells with hemocoel or salivary gland sporozoites and enumerated exoerythrocytic forms (EEFs) 24 and 48 h later ( Fig.…”

Section: Hemocoel Sporozoites Perform Continuous Gliding Locomotionmentioning

confidence: 58%

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Plasmodium berghei Sporozoites Acquire Virulence and Immunogenicity during Mosquito Hemocoel Transit

2014

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bMalaria is a vector-borne disease caused by the single-cell eukaryote Plasmodium. The infectious parasite forms are sporozoites, which originate from midgut-associated oocysts, where they eventually egress and reach the mosquito hemocoel. Sporozoites actively colonize the salivary glands in order to be transmitted to the mammalian host. Whether residence in the salivary glands provides distinct and vital cues for the development of infectivity remains unsolved. In this study, we systematically compared the infectivity of Plasmodium berghei sporozoites isolated from the mosquito hemocoel and salivary glands. Hemocoel sporozoites display a lower proportion of gliding motility but develop into liver stages when added to cultured hepatoma cells or after intravenous injection into mice. Mice infected by hemocoel sporozoites had blood infections similar to those induced by sporozoites liberated from salivary glands. These infected mice display indistinguishable systemic inflammatory cytokine responses and develop experimental cerebral malaria. When used as metabolically active, live attenuated vaccine, hemocoel sporozoites elicit substantial protection against sporozoite challenge infections. Collectively, these findings show that salivary gland colonization does not influence parasite virulence in the mammalian host when sporozoites are administered intravenously. This conclusion has important implications for in vitro sporozoite production and manufacturing of whole-sporozoite vaccines.

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Section: Discussionsupporting

confidence: 68%

Section: Hemocoel Sporozoites Perform Continuous Gliding Locomotionsupporting

confidence: 65%

Section: Hemocoel Sporozoites Perform Continuous Gliding Locomotionmentioning

confidence: 58%

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Plasmodium berghei Sporozoites Acquire Virulence and Immunogenicity during Mosquito Hemocoel Transit

2014

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“…These could interact with the sporozoite and slow it down even further by either increasing adhesion efficiency or by signaling. [22,27,36,37] This could be tested in pillar arrays or on flat substrates by linking the proteins covalently to the surface and comparing the speed of sporozoites gliding on these variable surfaces.…”

Section: Discussionmentioning

confidence: 99%

Microstructured Blood Vessel Surrogates Reveal Structural Tropism of Motile Malaria Parasites

Muthinja

Ripp

Hellmann

et al. 2017

Adv Healthcare Materials

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Muthinja, M. J. et al. (2017) Microstructured blood vessel surrogates reveal structural tropism of motile malaria parasites. Advanced Healthcare Materials, 6(6), 1601178. (doi:10.1002/adhm.201601178) There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it. This is the peer-reviewed version of the following article: Muthinja, M. J. et al. (2017) Investigating the association of sporozoites to pillars in arrays displaying pillars of different diameters revealed that the crescent-shaped parasites prefer to associate with and migrate around pillars with a similar curvature. This suggests that after transmission by a mosquito malaria parasites might use a structural tropism to recognize blood capillaries in the dermis in order to gain access to the blood stream.4

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“…However, an independent study reported a deficiency of TLP knock out parasites in cell Science Publications AJI traversal with no defect in gliding (Moreira et al, 2008). More recent studies have implicated the role of Heat Shock Protein 20 (HSP20) in regulating the function of cell traction and motility of sporozoites and ablation of HSP20 impaired migration in the host cells (Montagna et al, 2012).…”

Section: The Sporozoite Stage Molecular Motor and Host Cell Invasionmentioning

confidence: 99%

<i>PLASMODIUM</i> PRE-ERYTHROCYTIC STAGES: BIOLOGY, WHOLE PARASITE VACCINES AND TRANSGENIC MODELS

Kumar

Mishra

2012

American Journal of Immunology

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Malaria remains one of the world's worst health problems, which causes 216 million new cases and approximately 655,000 deaths every year WHO World Malaria Report, 2011. Malaria transmission to the mammalian host is initiated through a mosquito bite that delivers sporozoites into the vertebrate host. The injected sporozoites are selectively targeted to liver which is the first obligatory step in infection thus making this stage an attractive target for both drug and vaccine development. Research using rodent models of malaria has greatly facilitated the understanding of several aspects of pre-erythrocytic parasite biology and immunology. However, translation of this knowledge to combat Plasmodium falciparum infections still offers several challenges. We highlight in this review some of the recent advances in the field of Plasmodium sporozoite and liver stage biology and in the generation of whole organism attenuated vaccines. We also comment on the application of transgenic models central to Circumsporozoite Protein (CSP) in understanding the mechanism of pre-erythrocytic immunity.

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Critical Role for Heat Shock Protein 20 (HSP20) in Migration of Malarial Sporozoites

Cited by 60 publications

References 76 publications

Plasmodium berghei Sporozoites Acquire Virulence and Immunogenicity during Mosquito Hemocoel Transit

Plasmodium berghei Sporozoites Acquire Virulence and Immunogenicity during Mosquito Hemocoel Transit

Microstructured Blood Vessel Surrogates Reveal Structural Tropism of Motile Malaria Parasites

<i>PLASMODIUM</i> PRE-ERYTHROCYTIC STAGES: BIOLOGY, WHOLE PARASITE VACCINES AND TRANSGENIC MODELS

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