Malaria parasites form filamentous cell-to-cell connections during reproduction in the mosquito midgut

Malaria transmission blocking immunity has been found to operate against two distinct phases of development of malaria parasites in the mosquito midgut: (i) against the extracellular gametes and newly fertilized zygotes shortly after ingestion by a mosquito of parasitized blood and (ii) against the zygotes during their subsequent development into ookinetes. Immunity is antibody-mediated and stage-specific. A set of three proteins, synthesized in the gametocytes, expressed on the surface of the gametes and newly fertilized zygotes and subsequently shed during later transformation of the zygotes, has been identified as the target antigens of anti-gamete fertilization blocking antibodies. A single protein, synthesized and expressed on the zygote surface during its development to ookinetes, has been identified as the target of antibodies which block the development of the fertilized parasites in the mosquito. Immunization of hum an populations against gamete or zygote antigens, while not directly protecting an immunized individual from inflection, would reduce the transfer of malaria within the population. Such immunity, in addition to reducing the overall rate of malaria transmission, would, if combined with a vaccine against the asexual (disease-causing) stages, reduce the chance of selection of parasites that are resistant to the asexual vaccine by preventing their entry into the mosquito population.

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Malaria Parasites Co-opt Human Factor H to Prevent Complement-Mediated Lysis in the Mosquito Midgut

Cell Host & Microbe ◽

10.1016/j.chom.2012.11.013 ◽

2013 ◽

Vol 13 (1) ◽

pp. 29-41 ◽

Cited By ~ 54

Author(s):

Nina Simon ◽

Edwin Lasonder ◽

Matthias Scheuermayer ◽

Andrea Kuehn ◽

Sabrina Tews ◽

...

Keyword(s):

Human Factor ◽

Factor H ◽

Malaria Parasites ◽

Mosquito Midgut

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Motility precedes egress of malaria parasites from oocysts

eLife ◽

10.7554/elife.19157 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 20

Author(s):

Dennis Klug ◽

Friedrich Frischknecht

Keyword(s):

Salivary Gland ◽

Salivary Glands ◽

Specific Protein ◽

Anopheles Mosquito ◽

Vertebrate Host ◽

Malaria Parasites ◽

Mosquito Midgut ◽

Vital Component

Malaria is transmitted when an infected Anopheles mosquito deposits Plasmodium sporozoites in the skin during a bite. Sporozoites are formed within oocysts at the mosquito midgut wall and are released into the hemolymph, from where they invade the salivary glands and are subsequently transmitted to the vertebrate host. We found that a thrombospondin-repeat containing sporozoite-specific protein named thrombospondin-releated protein 1 (TRP1) is important for oocyst egress and salivary gland invasion, and hence for the transmission of malaria. We imaged the release of sporozoites from oocysts in situ, which was preceded by active motility. Parasites lacking TRP1 failed to migrate within oocysts and did not egress, suggesting that TRP1 is a vital component of the events that precede intra-oocyst motility and subsequently sporozoite egress and salivary gland invasion.

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Interaction between Host Complement and Mosquito-Midgut-Stage Plasmodium berghei

Infection and Immunity ◽

10.1128/iai.69.8.5064-5071.2001 ◽

2001 ◽

Vol 69 (8) ◽

pp. 5064-5071 ◽

Cited By ~ 44

Author(s):

Gabriele Margos ◽

Sandra Navarette ◽

Geoff Butcher ◽

Alex Davies ◽

Christine Willers ◽

...

Keyword(s):

Plasmodium Berghei ◽

Blood Cells ◽

Developmental Stages ◽

Alternative Pathway ◽

White Blood Cells ◽

Membrane Attack Complex ◽

Malaria Parasites ◽

Complement Components ◽

Ongoing Research ◽

Mosquito Midgut

ABSTRACT After ingestion by mosquitoes, gametocytes of malaria parasites become activated and form extracellular gametes that are no longer protected by the red blood cell membrane against immune effectors of host blood. We have studied the action of complement onPlasmodium developmental stages in the mosquito blood meal using the rodent malaria parasite Plasmodium berghei and rat complement as a model. We have shown that in the mosquito midgut, rat complement components necessary to initiate the alternative pathway (factor B, factor D, and C3) as well as C5 are present for several hours following ingestion of P. berghei-infected rat blood. In culture, 30 to 50% of mosquito midgut stages of P. berghei survived complement exposure during the first 3 h of development. Subsequently, parasites became increasingly sensitive to complement lysis. To investigate the mechanisms involved in their protection, we tested for C3 deposition on parasite surfaces and whether host CD59 (a potent inhibitor of the complement membrane attack complex present on red blood cells) was taken up by gametes while emerging from the host cell. Between 0.5 and 22 h, 90% of Pbs21-positive parasites were positive for C3. While rat red and white blood cells stained positive for CD59, Pbs21-positive parasites were negative for CD59. In addition, exposure of parasites to rat complement in the presence of anti-rat CD59 antibodies did not increase lysis. These data suggest that parasite or host molecules other than CD59 are responsible for the protection of malaria parasites against complement-mediated lysis. Ongoing research aims to identify these molecules.

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