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1.
Plasmodium sporozoites develop in oocysts on the midgut wall of the mosquito and are released into the hemocoel. Approximately 15-20% of oocyst sporozoites will successfully attach to and invade salivary glands, their target organ. We have previously shown that the major surface protein of sporozoites, the circumsporozoite (CS) protein, binds specifically to salivary glands and not to other mosquito organs exposed to circulating hemolymph. In addition, a peptide from the N-terminal portion of CS protein inhibits binding of the protein to the glands. In this study, we have extended these findings and show that both the protein and the peptide can inhibit sporozoite invasion of salivary glands. 相似文献
2.
Anke Harupa Brandon K. Sack Viswanathan Lakshmanan Nadia Arang Alyse N. Douglass Brian G. Oliver Andrew B. Stuart D. Noah Sather Scott E. Lindner Kevin Hybiske Motomi Torii Stefan H. I. Kappe 《Infection and immunity》2014,82(11):4643-4653
Plasmodium sporozoites develop within oocysts in the mosquito midgut wall and then migrate to the salivary glands. After transmission, they embark on a complex journey to the mammalian liver, where they infect hepatocytes. Proteins on the sporozoite surface likely mediate multiple steps of this journey, yet only a few sporozoite surface proteins have been described. Here, we characterize a novel, conserved sporozoite surface protein (SSP3) in the rodent malaria parasite Plasmodium yoelii. SSP3 is a putative type I transmembrane protein unique to Plasmodium. By using epitope tagging and SSP3-specific antibodies in conjunction with immunofluorescence microscopy, we showed that SSP3 is expressed in mosquito midgut oocyst sporozoites, exhibiting an intracellular localization. In sporozoites derived from the mosquito salivary glands, however, SSP3 localized predominantly to the sporozoite surface as determined by immunoelectron microscopy. However, the ectodomain of SSP3 appeared to be inaccessible to antibodies in nonpermeabilized salivary gland sporozoites. Antibody-induced shedding of the major surface protein circumsporozoite protein (CSP) exposed the SSP3 ectodomain to antibodies in some sporozoites. Targeted deletion of SSP3 adversely affected in vitro sporozoite gliding motility, which, surprisingly, impacted neither their cell traversal capacity, host cell invasion in vitro, nor infectivity in vivo. Together, these data reveal a previously unappreciated complexity of the Plasmodium sporozoite surface proteome and the roles of surface proteins in distinct biological activities of sporozoites. 相似文献
3.
Plasmodium berghei Sporozoites Acquire Virulence and Immunogenicity during Mosquito Hemocoel Transit
Malaria 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. 相似文献
4.
Plasmodium falciparum ookinetes migrate intercellularly throughAnopheles stephensi midgut epithelium
J. F. G. M. Meis G. Pool G. J. van Gemert A. H. W. Lensen T. Ponnudurai J. H. E. T. Meuwissen 《Parasitology research》1989,76(1):13-19
The migration ofPlasmodium falciparum andP. berghei ookinetes through the midgut epithelium inAnopheles stephensi was studied by transmission electron microscopy. With ruthenium red (RR) staining, the results of previous studies were confirmed:P. falciparum ookinetes take an intercellular route through the midgut epithelium. In the same mosquito species, the rodent parasiteP. berghei appeared to take an intracellular position, as previously suggested by other authors. The intra- or intercellular ookinete migration ofP. berghei orP. falciparum, respectively, can perhaps be related to the higher mortality ofP. berghei-infected mosquitoes within the first 2 days of infection. Evidence is presented that oocyst capsule formation begins as early as during the migration of the ookinete. After localization between the epithelial cells and the midgut basal lamina, the rapidly expanding oocyst stretches the overlying layer of the latter at the haemocoelic surface while a new basal lamina is generated between the oocyst and epithelial cell.Abbreviations
BL
basal lamina
-
CR
cristalloid
-
N
nucleus
-
RER
rough endoplasmic reticulum
-
Mp
malarial pigment
-
M
mitochondrion
-
MV
microvillous border
-
OC
oocyst capsule 相似文献
5.
J C Beier C N Oster J K Koros F K Onyango A K Githeko E Rowton D K Koech C R Roberts 《Journal of medical entomology》1989,26(6):547-553
Human circumsporozoite (CS) antibodies to Plasmodium falciparum were detected in blood meals from 45.0% of 1,547 field-collected Anopheles gambiae Giles sensu lato and Anopheles funestus Giles from western Kenya. Possible effects on malaria infections within the Anopheles host were investigated. Circumsporozoite antibodies were detected in blood meals up to 36 h after feeding. Antibodies crossing the midgut were detected experimentally in hemolymph from 4 to 36 h after feeding; human IgG also was present in hemolymph from fully gravid field-collected Anopheles. Ingestion of high-titer human CS antibodies or 2A10 monoclonal antibody to P. falciparum sporozoites by P. falciparum-infected An. gambiae, 10 d after feeding on an infected human, had no effect on o?cyst maturation, sporozoite rates, or sporozoite loads. Contact between CS antibodies and sporozoites in the hemocoel did not block sporozoite invasion of salivary glands. Human IgG antibodies were detected by an indirect fluorescent antibody technique on salivary gland sporozoites from 83.3% of 114 field-collected Anopheles. In 65.4% of 26 infections, antibodies persisted on sporozoites for at least three days. Thus, a high proportion of naturally infected An. gambiae s.l. and An. funestus in western Kenya transmit sporozoites that are bound with human IgG acquired during previous blood meals. The infectivity of such sporozoites needs to be determined in relation to natural transmission and to the potential use of malaria sporozoite vaccines. 相似文献
6.
Localization of circumsporozoite protein of Plasmodium ovale in midgut oocysts. 总被引:1,自引:0,他引:1
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H Nagasawa P M Procell C T Atkinson G H Campbell W E Collins M Aikawa 《Infection and immunity》1987,55(12):2928-2932
Circumsporozoite (CS) proteins are the major proteins found on the surface of salivary gland sporozoites and are the protective antigens of several species of malaria parasites. Little is known about the distribution of CS proteins in developing oocysts, however. Immunoelectron microscopy with protein A-gold and a monoclonal antibody specific for the CS protein of Plasmodium ovale was performed to investigate the distribution of CS protein within developing P. ovale oocysts. There was an almost complete absence of label in immature oocysts prior to the development of sporoblasts. In contrast, sporoblasts and budding and free sporozoites in mature oocysts were labeled uniformly on the outer surfaces of their plasma membranes, indicating a uniform distribution of CS protein on these membranes. Gold particles were frequently associated with the cytoplasm of sporoblasts and sporozoites, as well as with the inner surface of the oocyst capsule. This is the first evidence that CS protein is present in oocyst sporozoites and sporoblasts of P. ovale. 相似文献
7.
Yano K Otsuki H Arai M Komaki-Yasuda K Tsuboi T Torii M Kano S Kawazu S 《Molecular and biochemical parasitology》2008,159(2):142-145
To investigate the physiologic role of cytosolic 2-Cys peroxiredoxin of Plasmodium berghei (PbTPx-1), we infected the vector mosquito Anopheles stephensi with a parasite carrying a targeted knockout of pbtpx-1 (Prx-KO). The number of Prx-KO midgut oocysts at 14–15 days post-feeding (pf) was comparable to that of the parent strain (WT); however, the numbers of sporozoites that formed in midgut oocysts and accumulated in the salivary gland of Prx-KO-infected mosquitoes by 21 days pf were decreased to 10–20% and 3–10%, respectively, of those values in WT-infected mosquitoes. A higher frequency of DNA strand breaks was detected in Prx-KO oocysts than in WT oocysts. Sporozoites carrying the targeted disruption had reduced infectivity in mice; however, the knockout did not affect the ability of the sporozoite to reach the liver parenchyma and initiate exo-erythrocytic form (EEF) development. TPx-1 may be involved in development during exponentially multiplying stages, such as sporozoites and EEF. 相似文献
8.
Inhibition of malaria parasite development in mosquitoes by anti-mosquito-midgut antibodies. 总被引:3,自引:2,他引:3
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A A Lal M E Schriefer J B Sacci I F Goldman V Louis-Wileman W E Collins A F Azad 《Infection and immunity》1994,62(1):316-318
The mosquito midgut plays a central role in the development and subsequent transmission of malaria parasites. Using a rodent malaria parasite, Plasmodium berghei, and the mosquito vector Anopheles stephensi, we investigated the effect of anti-mosquito-midgut antibodies on the development of malaria parasites in the mosquito. In agreement with previous studies, we found that mosquitoes that ingested antimidgut antibodies along with infectious parasites had significantly fewer oocysts than mosquitoes in the control group. We also found that the antimidgut antibodies inhibit the development and/or translocation of the sporozoites. Together, these observations open an avenue for research toward the development of a vector-based malaria parasite transmission-blocking vaccine. 相似文献
9.
Sporozoites and free circumsporozoite (CS) protein were stained immunoenzymatically in 1-min saliva samples collected fromAnopheles stephensi mosquitoes infected with eitherPlasmodium berghei orP. falciparum. The number of sporozoites in 1-min saliva-streak samples significantly increased as the salivary gland index rose from 3+ to 4+. ForP. berghei-infected mosquitoes from which saliva had been collected before 30 days postfeed, the median sporozoite counts for 3+ and 4+ gland indexes were 4.5 and 116, respectively. ForP. falciparum-infected mosquitoes, the median counts obtained in two experiments were 4.5 and 14.5 (3+) and 97 and 107 (4+), respectively. The frequency of sporozoite detection in the saliva of mosquitoes containing <100 salivary-gland sporozoites was low (0.1), whereas that in the saliva of mosquitoes with >100 sporozoites was high (0.96). In highly infected 4+P. berghei-infected mosquitoes from which saliva had been collected after 30 days postinfection, both the volume of saliva collected and the median number of sporozoites recovered decreased significantly. 相似文献
10.
Coleman RE Barth JF Turell MJ Gordon SW Sattabongkot J Copeland R Wirtz RA 《Journal of medical entomology》2000,37(4):581-587
We developed a nitrocellulose-based, dipstick circumsporozoite (CS)-enzyme immunoassay [ELISA] for the simultaneous detection of Plasmodium falciparum and P. vivax-210 CS protein. The assay had a detection threshold of < 250 P. falciparum or 400 P. vivax sporozoites per sample, gave results concordant with dissection of salivary glands and CS-ELISA, but was slightly less sensitive than the CS-ELISA in microtiter plates. The assay consistently detected one infected mosquito in a pool of 10 or 20 mosquitoes, and was 100% specific in discriminating between species of Plasmodium when mosquito suspensions were spiked with sporozoites. The assay could be completed in 1 h, required no specialized equipment, and therefore was useful for field applications. 相似文献
11.
Preiser P Rénia L Singh N Balu B Jarra W Voza T Kaneko O Blair P Torii M Landau I Adams JH 《Infection and immunity》2004,72(6):3604-3608
MAEBL is a type 1 membrane protein that is implicated in the merozoite invasion of erythrocytes and sporozoite invasion of mosquito salivary glands. This apical organelle protein is structurally similar to the ebl erythrocyte binding proteins, such as EBA-175, except that the tandem ligand domains of MAEBL are similar to part of the extracellular domain of apical membrane antigen 1 and not the Duffy binding-like domain. Although midgut and salivary gland sporozoites are morphologically similar, salivary gland sporozoites undergo a period of new gene expression after infecting the salivary glands, display distinct phenotypic differences, and are more infectious for the mammalian host. The objectives of this project were to determine the molecular form of MAEBL in the infectious salivary gland sporozoites and whether the ligand has a role in the sporozoite development to exoerythrocytic stages in hepatocytes. We determined that MAEBL is newly expressed in salivary gland sporozoites and in a form distinct from what is present in the midgut sporozoites or present in erythrocytic stages. Both ligand domains (M1 and M2) were expressed as part of a full-length membrane form of MAEBL in the salivary gland sporozoites in contrast to the other stages that retain only the M2 ligand domain as part of the membrane form of the protein. Antisera developed against the cysteine-rich regions of the extracellular portion of MAEBL inhibited sporozoite development to exoerythrocytic forms in vitro. Together these data indicate that MAEBL has a role in this third developmental stage in the life cycle of the malaria parasite. Thus, MAEBL is another target for pre-erythrocytic-stage vaccine development against malaria parasites. 相似文献
12.
Summary A method is described wherebyP. berghei sprorozoites may be obtained from the salivary glands of infected femaleA. stephensi mosquitoes. The method is relatively easy to master, requires minimal handling of biological material, and is done with ordinary laboratory equipment. In addition, the sporozoites are rendered relatively free of contaminating micro-organisms and the entire operation may be performed aseptically. 相似文献
13.
High levels of plasma chitotriosidase are a marker of macrophage activation in several pathologies and, in particular, in
human malaria. Plasmodium falciparum, during its maturative cycle in the midgut of the Anopheles mosquito, secretes a chitinase to disrupt the peritrophic membrane, a necessary step in the migration of the parasite from
the midgut to the salivary glands of malaria’s vector. The cooperation between human chitotriosidase (Chit) and the chitinase
from P. falciparum in attacking the peritrophic membranes in the Anopheles midgut has been recently demonstrated by in vivo experiments. The present study confirms, by computational methods, this
functional homology. A simple sequence analysis method, potentially useful to assess fine textual closeness in families of
homologous proteins, is reported here and applied to a set of chitinases from mammals and plasmodia. This analysis confirms
the clustering and the phylogenetic relationships obtained with well-known alignment methods, but also shows that the sequences
of chitinases from malaria hosts and malaria parasites are correlated. This correlation, a sign of functional homology, is
discussed as a condition for the spreading of different forms of malaria. From this perspective, one can get insight into
the origins of malaria and its genetic or pharmacological control.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
14.
Antonia Herrera-OrtizJesús Martínez-Barnetche Nienke SmitMario H. Rodriguez Humberto Lanz-Mendoza 《Developmental and comparative immunology》2011,35(1):44-50
The expression of genes encoding the antimicrobial peptides (AMPs) attacin, cecropin and gambicin, as well as the effects of NO and H2O2 on their expression was investigated in midguts and fat bodies of Anopheles albimanus during the midgut infection with Plasmodium berghei. Midgut infection induced an increase in the expression of the three AMPs in both tissues; while NO and H2O2 were present in haemolymph. Treatment with L-NAME and vitamin C reduced the effect of P. berghei infection on the AMP's expression, and exogenous NO and H2O2 induced their expression in the mosquito fat body. The induction of AMPs in abdominal tissues, while the malaria parasites are in the mosquito midgut, suggests communication between the midgut epithelial cells and the abdominal tissue which has not yet had direct contact with the parasites. Free radical production in mosquito midgut and haemolymph during Plasmodium infection and their inductive effect on AMPs in abdominal tissues indicates the possible participation of these radicals in mediating a systemic immune response in this mosquito. 相似文献
15.
Direct microscopic quantification of dynamics of Plasmodium berghei sporozoite transmission from mosquitoes to mice 总被引:1,自引:0,他引:1
The number of malaria sporozoites delivered to a host by mosquitoes is thought to have a significant influence on the subsequent course of the infection in the mammalian host. We did studies with Anopheles stephensi mosquitoes with salivary gland infections of Plasmodium berghei sporozoites expressing a red fluorescent protein. After individual mosquitoes fed on an ear pinna or the ventral abdomen of a mouse, fluorescence microscopy was used to count numbers of sporozoites. Mosquitoes allowed to feed on the ear for periods of 3 versus 15 min deposited means of 281 versus 452 sporozoites, respectively, into the skin; this may have epidemiological implications because mosquitoes can feed for longer periods of time on sleeping hosts. Mosquitoes feeding on the ventral abdomen injected sporozoites not only into the skin but also into the underlying peritoneal musculature. Although mosquitoes injected fewer sporozoites into the abdominal tissues, more of these were reingested into the mosquito midgut, probably a consequence of easier access to blood intake from the abdominal area. The most consistent parameter of sporozoite transmission dynamics under all conditions of mosquito probing and feeding was the relatively slow release rate of sporozoites (approximately 1 to 2.5 per second) from the mosquito proboscis. The numbers of sporozoites introduced into the host by mosquitoes and the transmission efficiencies of sporozoite delivery are multifactorial phenomena that vary with length of probing time, skin site being fed upon, and numbers of sporozoites within the salivary glands. 相似文献
16.
17.
《Trends in immunology》2023,44(4):256-265
Malaria is caused by Plasmodium protozoa that are transmitted by anopheline mosquitoes. Plasmodium sporozoites are released with saliva when an infected female mosquito takes a blood meal on a vertebrate host. Sporozoites deposited into the skin must enter a blood vessel to start their journey towards the liver. After migration out of the mosquito, sporozoites are associated with, or in proximity to, many components of vector saliva in the skin. Recent work has elucidated how Anopheles saliva, and components of saliva, can influence host–pathogen interactions during the early stage of Plasmodium infection in the skin. Here, we discuss how components of Anopheles saliva can modulate local host responses and affect Plasmodium infectivity. We hypothesize that therapeutic strategies targeting mosquito salivary proteins can play a role in controlling malaria and other vector-borne diseases. 相似文献
18.
Gonzalez-Ceron L Rodriguez MH Santillan FV Hernandez JE Wirtz RA 《Journal of medical entomology》2000,37(3):331-334
The susceptibility to two coindigenous Plasmodium vivax Grassi & Feletti phenotypes VK210 and VK247 of three colonized Anopheles albimanus Wiedemann strains (white-striped, green and brown) from southern Mexico was investigated. Mosquitoes of the three strains were simultaneously fed with P. vivax-infected patient blood and examined 1 wk later for the presence of oocysts. The circumsporozoite protein phenotype type (VK210 and VK247) was determined by immunoflorescence of salivary gland sporozoites using monoclonal antibodies. The proportions of specimens infected and the number of oocyst per mosquito indicated that all mosquito strains were more susceptible to the phenotype VK210 than to VK247, but the white-striped strain was more susceptible to both parasite phenotypes than the other two strains. 相似文献
19.
Effects of magainins and cecropins on the sporogonic development of malaria parasites in mosquitoes. 总被引:12,自引:1,他引:12
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R W Gwadz D Kaslow J Y Lee W L Maloy M Zasloff L H Miller 《Infection and immunity》1989,57(9):2628-2633
Magainins and cecropins are families of peptides with broad antimicrobial and antiparasitic activities derived respectively from the skin of frogs or from giant silk moths. In insects, cecropins function as part of an inducible immune system against a number of bacterial infections. When injected into anopheline mosquitoes previously infected with a variety of Plasmodium species, both magainins and cecropins disrupt sporogonic development by aborting the normal development of oocysts; sporozoites are not formed and the vector cannot transmit the parasite to another host. It may be possible to induce effective transmission-blocking immunity in the mosquito vector by the introduction and expression of genes coding for magainins, cecropins, or similarly acting parasiticidal peptides into the mosquito genome. 相似文献
20.
Impact of transmission cycles and vector competence on global expansion and emergence of arboviruses
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Arboviruses are transmitted between arthropod vectors and vertebrate host. Arboviral infection in mosquitoes is initiated when a mosquito feeds on a viremic host. Following ingestion of a viremic blood meal by mosquitoes, virus enters midgut along with the blood, infects and replicates in midgut epithelial cells, and then escapes to the hemocoel, from where it disseminates to various secondary organs including salivary glands. Subsequently, when mosquito bites another host, a new transmission cycle is initiated. The midgut and salivary glands act as anatomical barriers to virus infection and escape. These complex interactions between the virus and vector dictate the vector competence. Thus, vector competence reflects the success in overcoming different barriers within the vector. Along with these, other intrinsic factors like midgut microbiota and immune responses, extrinsic factors like temperature and humidity, and genetic factors like vector genotype and viral genotype have been discussed in this review. Recent advancement on novel molecular tools to study vector competence is also included. Different modes of arboviral transmission like horizontal, vertical, and venereal and how these play role in sustenance and emergence of arboviruses in nature are also discussed. These factors can be exploited to reduce the susceptibility of vectors for the viruses, so as to control arboviral diseases to certain extent. 相似文献