During their development in mosquitoes, malaria parasites undergo massive losses that are in part due to a potent antiparasitic response mounted by the vector. The most efficient and best-characterized response relies on a complement-like system particularly effective against parasites as they cross the mosquito midgut epithelium. While our vision of the molecular and cellular events that lead to parasite elimination is still partial, our understanding of the steps triggering complement activation at the surface of invading parasites has considerably progressed, not only through the identification of novel contributing genes, but also with the recent in-depth characterization of the different mosquito blood cell types, and the ability to track them in live mosquitoes. Here, we propose a simple model based on the time of invasion to explain how parasites may escape complement-like responses during midgut infection.
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http://dx.doi.org/10.1016/j.mib.2023.102280 | DOI Listing |
Nat Commun
June 2024
Department of Microbiology & Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Cholesterol-dependent cytolysins (CDCs) comprise a large family of pore-forming toxins produced by Gram-positive bacteria, which are used to attack eukaryotic cells. Here, we functionally characterize a family of 2-component CDC-like (CDCL) toxins produced by the Gram-negative Bacteroidota that form pores by a mechanism only described for the mammalian complement membrane attack complex (MAC). We further show that the Bacteroides CDCLs are not eukaryotic cell toxins like the CDCs, but instead bind to and are proteolytically activated on the surface of closely related species, resulting in pore formation and cell death.
View Article and Find Full Text PDFBiochemistry
March 2024
Department of Anesthesiology, University of California at San Diego, La Jolla, California 92093, United States.
Schwann cells (SCs) undergo phenotypic transformation and then orchestrate nerve repair following a peripheral nervous system injury. The low-density lipoprotein receptor-related protein-1 (LRP1) is significantly upregulated in SCs in response to acute injury, activating cJun and promoting SC survival. Matrix-metalloproteinase-9 (MMP-9) is an LRP1 ligand that binds LRP1 through its hemopexin domain (PEX) and activates SC survival signaling and migration.
View Article and Find Full Text PDFPLoS Pathog
February 2024
Institut Pasteur, Université de Paris, CNRS UMR2000, Unit of Genetics and Genomics of Insect Vectors, Department of Parasites and Insect Vectors, Paris, France.
Leucine-rich repeat (LRR) proteins are commonly involved in innate immunity of animals and plants, including for pattern recognition of pathogen-derived elicitors. The Anopheles secreted LRR proteins APL1C and LRIM1 are required for malaria ookinete killing in conjunction with the complement-like TEP1 protein. However, the mechanism of parasite immune recognition by the mosquito remains unclear, although it is known that TEP1 lacks inherent binding specificity.
View Article and Find Full Text PDFCurr Opin Microbiol
April 2023
Université de Strasbourg, CNRS, Inserm, UPR9022/U1257, Mosquito Immune Responses (MIR), F-67000 Strasbourg, France. Electronic address:
During their development in mosquitoes, malaria parasites undergo massive losses that are in part due to a potent antiparasitic response mounted by the vector. The most efficient and best-characterized response relies on a complement-like system particularly effective against parasites as they cross the mosquito midgut epithelium. While our vision of the molecular and cellular events that lead to parasite elimination is still partial, our understanding of the steps triggering complement activation at the surface of invading parasites has considerably progressed, not only through the identification of novel contributing genes, but also with the recent in-depth characterization of the different mosquito blood cell types, and the ability to track them in live mosquitoes.
View Article and Find Full Text PDFDev Comp Immunol
March 2023
College of Life Sciences, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China. Electronic address:
As the most primitive vertebrates, lampreys are significant in understanding the early origin and evolution of the vertebrate innate and adaptive immune systems. The complement system is a biological response system with complex and precise regulatory mechanisms and plays an important role in innate and adaptive immunity. It consists of more than 30 distinct components, including intrinsic components, regulatory factors, and complement receptors.
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