蚊子对疟原虫的免疫机制

在防治疟疾感染的研究中,蚊子对疟原虫免疫机制的研究成为目前的研究热点。蚊子对疟原虫的免疫主要包括：血细胞介导的体液和细胞反应,丝氨酸蛋白酶介导的免疫防御反应,前酚氧化酶级联反应介导的黑化包被和蚊子体内免疫基因的活化。尤其是近来在蚊子体内免疫基因研究方面所取得的突破性进展,为人类控制疟疾及最终消灭疟疾提供了非常有价值的资料。     

Existing Infection Facilitates Establishment and Density of Malaria Parasites in Their Mosquito Vector

Very little is known about how vector-borne pathogens interact within their vector and how this impacts transmission. Here we show that mosquitoes can accumulate mixed strain malaria infections after feeding on multiple hosts. We found that parasites have a greater chance of establishing and reach higher densities if another strain is already present in a mosquito. Mixed infections contained more parasites but these larger populations did not have a detectable impact on vector survival. Together these results suggest that mosquitoes taking multiple infective bites may disproportionally contribute to malaria transmission. This will increase rates of mixed infections in vertebrate hosts, with implications for the evolution of parasite virulence and the spread of drug-resistant strains. Moreover, control measures that reduce parasite prevalence in vertebrate hosts will reduce the likelihood of mosquitoes taking multiple infective feeds, and thus disproportionally reduce transmission. More generally, our study shows that the types of strain interactions detected in vertebrate hosts cannot necessarily be extrapolated to vectors.     

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

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Highlights? Malaria gametes evade human complement by binding factor H ? The plasmodial protein PfGAP50 binds to factor H on the gamete surface ? Binding of factor H results in inactivation of the complement protein C3b ? Functional inhibition of factor H or PfGAP50 reduces parasite transmission to the mosquito     

Glutathione Reductase-null Malaria Parasites Have Normal Blood Stage Growth but Arrest during Development in the Mosquito

Malaria parasites contain a complete glutathione (GSH) redox system, and several enzymes of this system are considered potential targets for antimalarial drugs. Through generation of a γ-glutamylcysteine synthetase (γ-GCS)-null mutant of the rodent parasite Plasmodium berghei, we previously showed that de novo GSH synthesis is not critical for blood stage multiplication but is essential for oocyst development. In this study, phenotype analyses of mutant parasites lacking expression of glutathione reductase (GR) confirmed that GSH metabolism is critical for the mosquito oocyst stage. Similar to what was found for γ-GCS, GR is not essential for blood stage growth. GR-null parasites showed the same sensitivity to methylene blue and eosin B as wild type parasites, demonstrating that these compounds target molecules other than GR in Plasmodium. Attempts to generate parasites lacking both GR and γ-GCS by simultaneous disruption of gr and γ-gcs were unsuccessful. This demonstrates that the maintenance of total GSH levels required for blood stage survival is dependent on either de novo GSH synthesis or glutathione disulfide (GSSG) reduction by Plasmodium GR. Our studies provide new insights into the role of the GSH system in malaria parasites with implications for the development of drugs targeting GSH metabolism.     

Enzyme Typing of Malaria Parasites

Analysis of various isolates of Plasmodium falciparum from East and West Africa and from South-east Asia showed that some of the parasite enzymes can exist in more than one electrophoretic form. At least one form of each enzyme was common to parasites from all three regions. The enzyme forms could be used to differentiate morphologically indistinguishable samples of P. falciparum.     

Malaria Parasites of Toucans*

SYNOPSIS. Of 2 species of malaria parasites described from the toco toucan (Ramphastos toco), one (Plasmodium huffi) has been thought to be of doubtful validity, mainly because the erythrocytic cycle was said to include 2 distinct types of segmenters, varying greatly in size and fecundity. We recently found a parasite in a Swainson's toucan (R. swainsonii) which seems the same as the smaller component of P. huffi, and a 2nd small species of Plasmodium, apparently P. rouxi, in the blood of a sulfur-breasted toucan (R. s. sulfuratus). Unlike P. huffi, the former is easily transmissible by blood inoculation to canaries, in which it causes a highly fatal infection. It resembles P. nucleophilum structurally, tho there are minor differences. We propose to call it Plasmodium nucleophilum tucani. In sharp contrast to P. huffi, only mature erythrocytes in the blood are parasitized. Death of infected canaries seems to be the result of massive invasion of the internal organs, especially lungs and brain, by exoerythrocytic stages. A number of other bird species, among them the common jungle babbler, lesser hill mynah, ring-necked and sacred white dove, common pigeon, and Indian hill partridge (chukar) proved essentially refractory, but the collared aracari developed a mild infection much like that observed in toucans. Two young sulfur-breasted toucans failed to become infected when given heavy dosages of blood from a blue-eared glossy starling having a naturally acquired infection of Plasmodium nucleophilum, of the type occurring in passerines.     

Genetics of Mosquito Vector Competence

Mosquito-borne diseases are responsible for significant human morbidity and mortality throughout the world. Efforts to control mosquito-borne diseases have been impeded, in part, by the development of drug-resistant parasites, insecticide-resistant mosquitoes, and environmental concerns over the application of insecticides. Therefore, there is a need to develop novel disease control strategies that can complement or replace existing control methods. One such strategy is to generate pathogen-resistant mosquitoes from those that are susceptible. To this end, efforts have focused on isolating and characterizing genes that influence mosquito vector competence. It has been known for over 70 years that there is a genetic basis for the susceptibility of mosquitoes to parasites, but until the advent of powerful molecular biological tools and protocols, it was difficult to assess the interactions of pathogens with their host tissues within the mosquito at a molecular level. Moreover, it has been only recently that the molecular mechanisms responsible for pathogen destruction, such as melanotic encapsulation and immune peptide production, have been investigated. The molecular characterization of genes that influence vector competence is becoming routine, and with the development of the Sindbis virus transducing system, potential antipathogen genes now can be introduced into the mosquito and their effect on parasite development can be assessed in vivo. With the recent successes in the field of mosquito germ line transformation, it seems likely that the generation of a pathogen-resistant mosquito population from a susceptible population soon will become a reality.     

Quantifying Transmission Investment in Malaria Parasites

Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.