Invasion of mosquito salivary glands by malaria parasites: Prerequisites and defense strategies

Mueller, Ann‐Kristin; Kohlhepp, Florian; Hammerschmidt, Christiane; Michel, Kristin

doi:10.1016/j.ijpara.2010.05.005

Cited by 58 publications

(42 citation statements)

References 95 publications

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“…A similar strong epithelial response was reported in the mosquito midgut epithelium when invaded by the Plasmodium ookinetes [75, 100]. In contrast, Plasmodium sporozoite invasion of the salivary glands did not have a drastic impact on the epithelial cells [101]. The T. brucei attachment to the salivary gland epithelium is an essential event for the parasite in the maintenance of its life cycle as it ensures that the tsetse saliva remains trypanosome-infected during the whole life span of the fly.…”

Section: Resultsmentioning

confidence: 56%

Tsetse fly tolerance to T. brucei infection: transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland

2016

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BackgroundFor their transmission, African trypanosomes rely on their blood feeding insect vector, the tsetse fly (Glossina sp.). The ingested Trypanosoma brucei parasites have to overcome a series of barriers in the tsetse fly alimentary tract to finally develop into the infective metacyclic forms in the salivary glands that are transmitted to a mammalian host by the tsetse bite. The parasite population in the salivary gland is dense with a significant number of trypanosomes tightly attached to the epithelial cells. Our current knowledge on the impact of the infection on the salivary gland functioning is very limited. Therefore, this study aimed to gain a deeper insight into the global gene expression changes in the salivary glands of Glossina morsitans morsitans in response to an infection with the T. brucei parasite. A detailed whole transcriptome comparison of midgut-infected tsetse with and without a mature salivary gland infection was performed to study the impact of a trypanosome infection on different aspects of the salivary gland functioning and the mechanisms that are induced in this tissue to tolerate the infection i.e. to control the negative impact of the parasite presence. Moreover, a transcriptome comparison with age-matched uninfected flies was done to see whether gene expression in the salivary glands is already affected by a trypanosome infection in the tsetse midgut.ResultsBy a RNA-sequencing (RNA-seq) approach we compared the whole transcriptomes of flies with a T. brucei salivary gland/midgut infection versus flies with only a midgut infection or versus non-infected flies, all with the same age and feeding history. More than 7500 salivary gland transcripts were detected from which a core group of 1214 differentially expressed genes (768 up- and 446 down-regulated) were shared between the two transcriptional comparisons. Gene Ontology enrichment analysis and detailed gene expression comparisons showed a diverse impact at the gene transcript level. Increased expression was observed for transcripts encoding for proteins involved in immunity (like several genes of the Imd-signaling pathway, serine proteases, serpins and thioester-containing proteins), detoxification of reactive species, cell death, cytoskeleton organization, cell junction and repair. Decreased expression was observed for transcripts encoding the major secreted proteins such as 5′-nucleotidases, adenosine deaminases and the nucleic acid binding proteins Tsals. Moreover, expression of some gene categories in the salivary glands were found to be already affected by a trypanosome midgut infection, before the parasite reaches the salivary glands.ConclusionsThis study reveals that the T. brucei population in the tsetse salivary gland has a negative impact on its functioning and on the integrity of the gland epithelium. Our RNA-seq data suggest induction of a strong local tissue response in order to control the epithelial cell damage, the ROS intoxication of the cellular environment and the parasite infection, resulting in the fly tolera...

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Section: Resultsmentioning

confidence: 56%

Tsetse fly tolerance to T. brucei infection: transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland

2016

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“…Salivary gland invasion is essential for malaria transmission and requires sporozoite attachment to the basal lamina of salivary glands, invasion of gland cells, followed by migration into the secretory cavity (reviewed in Mueller, Kohlhepp, Hammerschmidt, & Michel, 2010;Smith & Jacobs-Lorena, 2010). Salivary gland invasion is essential for malaria transmission and requires sporozoite attachment to the basal lamina of salivary glands, invasion of gland cells, followed by migration into the secretory cavity (reviewed in Mueller, Kohlhepp, Hammerschmidt, & Michel, 2010;Smith & Jacobs-Lorena, 2010).…”

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confidence: 99%

Rhoptry neck protein 2 expressed in Plasmodium sporozoites plays a crucial role during invasion of mosquito salivary glands

Ishino

Murata

Tokunaga

et al. 2018

Cellular Microbiology

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Malaria parasite transmission to humans is initiated by the inoculation of Plasmodium sporozoites into the skin by mosquitoes. Sporozoites develop within mosquito midgut oocysts, first invade the salivary glands of mosquitoes, and finally infect hepatocytes in mammals. The apical structure of sporozoites is conserved with the infective forms of other apicomplexan parasites that have secretory organelles, such as rhoptries and micronemes. Because some rhoptry proteins are crucial for Plasmodium merozoite infection of erythrocytes, we examined the roles of rhoptry proteins in sporozoites. Here, we demonstrate that rhoptry neck protein 2 (RON2) is also localized to rhoptries in sporozoites. To elucidate RON2 function in sporozoites, we applied a promoter swapping strategy to restrict ron2 transcription to the intraerythrocytic stage in the rodent malaria parasite, Plasmodium berghei. Ron2 knockdown sporozoites were severely impaired in their ability to invade salivary glands, via decreasing the attachment capacity to the substrate. This is the first rhoptry protein demonstrated to be involved in salivary gland invasion. In addition, ron2 knockdown sporozoites showed less infectivity to hepatocytes, possibly due to decreased attachment/gliding ability, indicating that parts of the parasite invasion machinery are conserved, but their contribution might differ among infective forms. Our sporozoite stage‐specific knockdown system will help to facilitate understanding the comprehensive molecular mechanisms of parasite invasion of target cells.

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“…Sporozoite invasion of mosquito SGs is receptor-mediated, and involves several parasite and SG proteins 10, 11 . Characterization of the salivary components involved in parasite infection and transmission would greatly enhance our understanding of the mosquito–host–pathogen interface, and potentially reveal candidate targets for malaria prevention and control.…”

Section: Introductionmentioning

confidence: 99%

Solute carriers affect Anopheles stephensi survival and Plasmodium berghei infection in the salivary glands

Couto

Antunes

Pinheiro-Silva

et al. 2017

Sci Rep

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Malaria is caused by mosquito-borne Plasmodium spp. parasites that must infect and survive within mosquito salivary glands (SGs) prior to host transmission. Recent advances in transcriptomics and the complete genome sequencing of mosquito vectors have increased our knowledge of the SG genes and proteins involved in pathogen infection and transmission. Membrane solute carriers are key proteins involved in drug transport and are useful in the development of new interventions for transmission blocking. Herein, we applied transcriptomics analysis to compare SGs mRNA levels in Anopheles stephensi fed on non-infected and P. berghei-infected mice. The A. stephensi solute carriers prestinA and NDAE1 were up-regulated in response to infection. These molecules are predicted to interact with each other, and are reportedly involved in the maintenance of cell homeostasis. To further evaluate their functions in mosquito survival and parasite infection, these genes were knocked down by RNA interference. Knockdown of prestinA and NDAE1 resulted in reduction of the number of sporozoites in mosquito SGs. Moreover, NDAE1 knockdown strongly impacted mosquito survival, resulting in the death of half of the treated mosquitoes. Overall, our findings indicate the importance of prestinA and NDAE1 in interactions between mosquito SGs and Plasmodium, and suggest the need for further research.Over the last 15 years, massive prevention measures and new treatment tools have greatly decreased the global malaria burden. However, despite these advances, about 214 million new malaria cases and 438,000 associated deaths were registered in 2015 alone 1 . Malaria is caused by mosquito-borne Plasmodium parasites. In particular, adult female mosquitoes of the genus Anopheles are efficient Plasmodium vectors in many diverse ecosystems 2, 3 . Anopheles stephensi is a competent vector for both Plasmodium falciparum and P. vivax, the most virulent malaria-associated species 3 , as well as for Plasmodium species that infect rodents and, thus, this mosquito species is widely used as a laboratory model. A. stephensi is found throughout the Indian subcontinent-with its territory extending from the Arabian Peninsula, Iran, and Iraq, to Bangladesh, southern China, Myanmar, and Thailand 4 .Malaria transmission from mosquitoes to vertebrate hosts occurs through the mosquito's salivary glands (SGs), and for this reason many studies have focused on this organ to develop new malaria control measures [5][6][7][8][9] . Sporozoite invasion of mosquito SGs is receptor-mediated, and involves several parasite and SG proteins 10,11 . Characterization of the salivary components involved in parasite infection and transmission would greatly enhance our understanding of the mosquito-host-pathogen interface, and potentially reveal candidate targets for malaria prevention and control.

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Invasion of mosquito salivary glands by malaria parasites: Prerequisites and defense strategies

Cited by 58 publications

References 95 publications

Tsetse fly tolerance to T. brucei infection: transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland

Tsetse fly tolerance to T. brucei infection: transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland

Rhoptry neck protein 2 expressed in Plasmodium sporozoites plays a crucial role during invasion of mosquito salivary glands

Solute carriers affect Anopheles stephensi survival and Plasmodium berghei infection in the salivary glands

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