title: Reduced parasite motility and micronemal protein secretion by a p38 MAPK inhibitor leads to a severe impairment of cell invasion by the apicomplexan parasite Eimeria tenella.
abstract: E. tenella infection is associated with a severe intestinal disease leading to high economic losses in poultry industry. Mitogen activated protein kinases (MAPKs) are implicated in early response to infection and are divided in three pathways: p38, extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK). Our objective was to determine the importance of these kinases on cell invasion by E. tenella. We evaluated the effect of specific inhibitors (ERK: PD98059, JNKII: SP600125, p38 MAPK: SB203580) on the invasion of epithelial cells. Incubation of SP600125 and SB203580 with epithelial cells and parasites significantly inhibited cell invasion with the highest degree of inhibition (90%) for SB203580. Silencing of the host p38α MAPK expression by siRNA led to only 20% decrease in cell invasion. In addition, when mammalian epithelial cells were pre-treated with SB203580, and washed prior infection, a 30% decrease in cell invasion was observed. This decrease was overcome when a p38 MAPK activator, anisomycin was added during infection. This suggests an active but limited role of the host p38 MAPK in this process. We next determined whether SB203580 has a direct effect on the parasite. Indeed, parasite motility and secretion of micronemal proteins (EtMIC1, 2, 3 and 5) that are involved in cell invasion were both decreased in the presence of the inhibitor. After chasing the inhibitor, parasite motility and secretion of micronemal proteins were restored and subsequently cell invasion. SB203580 inhibits cell invasion by acting partly on the host cell and mainly on the parasite.
authors.affiliation: Apicomplexes et Immunité Mucosale, INRA, UMR1282, Infectiologie et Santé Publique, F-37380 Nouzilly, France; Université François Rabelais de Tours, UMR1282, Infectiologie et Santé Publique, F-37000 Tours, France.
authors.forename: Françoise I
authors.initials: FI
authors.lastname: Bussière
authors.affiliation: Apicomplexes et Immunité Mucosale, INRA, UMR1282, Infectiologie et Santé Publique, F-37380 Nouzilly, France; Université François Rabelais de Tours, UMR1282, Infectiologie et Santé Publique, F-37000 Tours, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Brossier
authors.affiliation: Université François Rabelais de Tours, UMR1282, Infectiologie et Santé Publique, F-37000 Tours, France; Plate-forme d'Analyse Intégrative des Biomolécules, Laboratoire de Cytométrie et Fluorimétrie, INRA, UMR1282, Infectiologie et Santé Publique, F-37380 Nouzilly, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Vern
authors.affiliation: Apicomplexes et Immunité Mucosale, INRA, UMR1282, Infectiologie et Santé Publique, F-37380 Nouzilly, France; Université François Rabelais de Tours, UMR1282, Infectiologie et Santé Publique, F-37000 Tours, France.
authors.forename: Alisson
authors.initials: A
authors.lastname: Niepceron
authors.affiliation: Apicomplexes et Immunité Mucosale, INRA, UMR1282, Infectiologie et Santé Publique, F-37380 Nouzilly, France; Université François Rabelais de Tours, UMR1282, Infectiologie et Santé Publique, F-37000 Tours, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Silvestre
authors.affiliation: Apicomplexes et Immunité Mucosale, INRA, UMR1282, Infectiologie et Santé Publique, F-37380 Nouzilly, France; Université François Rabelais de Tours, UMR1282, Infectiologie et Santé Publique, F-37000 Tours, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: de Sablet
authors.affiliation: Apicomplexes et Immunité Mucosale, INRA, UMR1282, Infectiologie et Santé Publique, F-37380 Nouzilly, France; Université François Rabelais de Tours, UMR1282, Infectiologie et Santé Publique, F-37000 Tours, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Lacroix-Lamandé
authors.affiliation: Apicomplexes et Immunité Mucosale, INRA, UMR1282, Infectiologie et Santé Publique, F-37380 Nouzilly, France; Université François Rabelais de Tours, UMR1282, Infectiologie et Santé Publique, F-37000 Tours, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Laurent
mesh_terms: D000595:Amino Acid Sequence; D004305:Dose-Response Relationship, Drug; D016786:Eimeria tenella / Q000187:drug effects* / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000469:parasitology; D048688:MAP Kinase Kinase 7 / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D015800:Protozoan Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7