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Hemocyte Differentiation Mediates The Mosquito Late-Phase Immune Response Against Plasmodium In Anopheles Gambiae, Ryan C. Smith, Carolina Barillas-Mury, Marcelo Jacobs-Lorena
Hemocyte Differentiation Mediates The Mosquito Late-Phase Immune Response Against Plasmodium In Anopheles Gambiae, Ryan C. Smith, Carolina Barillas-Mury, Marcelo Jacobs-Lorena
Ryan C. Smith
Plasmodium parasites must complete development in the mosquito vector for transmission to occur. The mosquito innate immune response is remarkably efficient in limiting parasite numbers. Previous work has identified a LPS-induced TNFα transcription factor (LITAF)-like transcription factor, LITAF-like 3 (LL3), which significantly influences parasite numbers. Here, we demonstrate that LL3 does not influence invasion of the mosquito midgut epithelium or ookinete-to-oocyst differentiation but mediates a late-phase immune response that decreases oocyst survival. LL3 expression in the midgut and hemocytes is activated by ookinete midgut invasion and is independent of the mosquito microbiota, suggesting that LL3 may be a component of …
The Plasmodium Bottleneck: Malaria Parasite Losses In The Mosquito Vector, Ryan C. Smith, Joel Vega-Rodríguez, Marcelo Jacobs-Lorena
The Plasmodium Bottleneck: Malaria Parasite Losses In The Mosquito Vector, Ryan C. Smith, Joel Vega-Rodríguez, Marcelo Jacobs-Lorena
Ryan C. Smith
Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission.
Immunization Against A Merozoite Sheddase Promotes Multiple Invasion Of Red Blood Cells And Attenuates Plasmodium Infection In Mice, Ryan C. Smith, Daisy D. Colón-López, Jürgen Bosch
Immunization Against A Merozoite Sheddase Promotes Multiple Invasion Of Red Blood Cells And Attenuates Plasmodium Infection In Mice, Ryan C. Smith, Daisy D. Colón-López, Jürgen Bosch
Ryan C. Smith
Subtilisin-like protease 2 (SUB2) is a conserved serine protease utilized by Plasmodium parasites as a surface sheddase required for successful merozoite invasion of host red blood cells and has been implicated in ookinete invasion of the mosquito midgut. To determine if SUB2 is a suitable vaccine target to interfere with malaria parasite development, the effects of SUB2-immunization on the Plasmodium life cycle were examined in its vertebrate and invertebrate hosts. Swiss Webster mice were immunized with SUB2 peptides conjugated to Keyhole limpet hemocyanin (KLH) or KLH alone, and then challenged with Plasmodium berghei. To determine the effects of immunization on …
Transgenic Mosquitoes Expressing A Phospholipase A(2) Gene Have A Fitness Advantage When Fed Plasmodium Falciparum-Infected Blood, Ryan C. Smith, Christopher Kizito, Jason L. Rasgon, Marcelo Jacobs-Lorena
Transgenic Mosquitoes Expressing A Phospholipase A(2) Gene Have A Fitness Advantage When Fed Plasmodium Falciparum-Infected Blood, Ryan C. Smith, Christopher Kizito, Jason L. Rasgon, Marcelo Jacobs-Lorena
Ryan C. Smith
Genetically modified mosquitoes have been proposed as an alternative strategy to reduce the heavy burden of malaria. In recent years, several proof-of-principle experiments have been performed that validate the idea that mosquitoes can be genetically modified to become refractory to malaria parasite development. We have created two transgenic lines of Anophelesstephensi, a natural vector of Plasmodium falciparum, which constitutively secrete a catalytically inactive phospholipase A2 (mPLA2) into the midgut lumen to interfere with Plasmodium ookinete invasion. Our experiments show that both transgenic lines expressing mPLA2 significantly impair the development of rodent malaria parasites, but only one line impairs the development …
Enterobacter-Activated Mosquito Immune Responses To Plasmodium Involve Activation Of Srpn6 In Anopheles Stephensi, Ryan C. Smith, Abraham G. Eappen, Marcelo Jacobs-Lorena
Enterobacter-Activated Mosquito Immune Responses To Plasmodium Involve Activation Of Srpn6 In Anopheles Stephensi, Ryan C. Smith, Abraham G. Eappen, Marcelo Jacobs-Lorena
Ryan C. Smith
Successful development of Plasmodium in the mosquito is essential for the transmission of malaria. A major bottleneck in parasite numbers occurs during midgut invasion, partly as a consequence of the complex interactions between the endogenous microbiota and the mosquito immune response. We previously identified SRPN6 as an immune component which restricts Plasmodium berghei development in the mosquito. Here we demonstrate that SRPN6 is differentially activated by bacteria in Anopheles stephensi, but only when bacteria exposure occurs on the lumenal surface of the midgut epithelium. Our data indicate that AsSRPN6 is strongly induced following exposure to Enterobacter cloacae, a common component …
Regulation Of Anti-Plasmodium Immunity By A Litaf-Like Transcription Factor In The Malaria Vector Anopheles Gambiae, Ryan C. Smith, Abraham G. Eappen, Andrea J. Radtke, Marcelo Jacobs-Lorena
Regulation Of Anti-Plasmodium Immunity By A Litaf-Like Transcription Factor In The Malaria Vector Anopheles Gambiae, Ryan C. Smith, Abraham G. Eappen, Andrea J. Radtke, Marcelo Jacobs-Lorena
Ryan C. Smith
The mosquito is the obligate vector for malaria transmission. To complete its development within the mosquito, the malaria parasite Plasmodium must overcome the protective action of the mosquito innate immune system. Here we report on the involvement of the Anopheles gambiae orthologue of a conserved component of the vertebrate immune system, LPS-induced TNFα transcription factor (LITAF), and its role in mosquito anti-Plasmodium immunity. An. gambiae LITAF-like 3 (LL3) expression is up-regulated in response to midgut invasion by both rodent and human malaria parasites. Silencing of LL3 expression greatly increases parasite survival, indicating that LL3 is part of an anti-Plasmodium defense …