title: Plasmodium falciparum merozoite surface protein 1 blocks the proinflammatory protein S100P.
abstract: The malaria parasite, Plasmodium falciparum, and the human immune system have coevolved to ensure that the parasite is not eliminated and reinfection is not resisted. This relationship is likely mediated through a myriad of host-parasite interactions, although surprisingly few such interactions have been identified. Here we show that the 33-kDa fragment of P. falciparum merozoite surface protein 1 (MSP1(33)), an abundant protein that is shed during red blood cell invasion, binds to the proinflammatory protein, S100P. MSP1(33) blocks S100P-induced NFκB activation in monocytes and chemotaxis in neutrophils. Remarkably, S100P binds to both dimorphic alleles of MSP1, estimated to have diverged >27 Mya, suggesting an ancient, conserved relationship between these parasite and host proteins that may serve to attenuate potentially damaging inflammatory responses.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. waisbergm@niaid.nih.gov
authors.forename: Michael
authors.initials: M
authors.lastname: Waisberg
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Cerqueira
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Yager
authors.forename: Ivo M B
authors.initials: IM
authors.lastname: Francischetti
authors.forename: Jinghua
authors.initials: J
authors.lastname: Lu
authors.forename: Nidhi
authors.initials: N
authors.lastname: Gera
authors.forename: Prakash
authors.initials: P
authors.lastname: Srinivasan
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Balazs
authors.initials: B
authors.lastname: Rada
authors.forename: Jan
authors.initials: J
authors.lastname: Lukszo
authors.forename: Kent D
authors.initials: KD
authors.lastname: Barbian
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Leto
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.forename: David L
authors.initials: DL
authors.lastname: Narum
authors.forename: Najib
authors.initials: N
authors.lastname: El-Sayed
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Susan K
authors.initials: SK
authors.lastname: Pierce
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020066:Merozoite Surface Protein 1 / Q000502:physiology*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010963:Plasmodium falciparum / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance
chemical_list: D002135:Calcium-Binding Proteins; D020066:Merozoite Surface Protein 1; D009363:Neoplasm Proteins; C103003:S100P protein, human