Journal of Parasitology Research Host Parasite Interaction Host Parasite Interaction Journal of Parasitology Research Host Parasite Interaction Copyright © 2011 Hindawi Publishing Corporation. All rights reserved. This is a focus issue published in volume 2011 of “Journal of Parasitology Research.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board Takeshi Agatsuma, Japan Ana Maria Jansen, Brazil Barbara Papadopoulou, Canada Jeffrey Bethony, USA MariaV.Johansen,Denmark A. F. Petavy, France D. D. Chadee, USA Nirbhay Kumar, USA Benjamin M. Rosenthal, USA Kwang Poo Chang, USA Michael Lanzer, Germany Joseph Schrevel, France Wej Choochote, Thailand D. S. Lindsay, USA Jose´ F. Silveira, Brazil Alvin A. Gajadhar, Canada Bernard Marchand, France M. J. Stear, UK C. Genchi, Italy Renato A. Mortara, Brazil Xin-zhuan Su, USA Boyko B. Georgiev, Bulgaria Domenico Otranto, Italy Kazuyuki Tanabe, Japan Contents A Sequential Model of Host Cell Killing and Phagocytosis by Entamoeba histolytica, Adam Sateriale and Christopher D. Huston Volume 2011, Article ID 926706, 10 pages Malaria Vaccine Development: Are Bacterial Flagellin Fusion Proteins the Bridge between Mouse and Humans?, Daniel Y. Bargieri, Irene S. Soares, Fabio T. M. Costa, Catarina J. Braga, Luis C. S. Ferreira, and Mauricio M. Rodrigues Volume 2011, Article ID 965369, 10 pages The Influence of MHC and Immunoglobulins A and E on Host Resistance to Gastrointestinal Nematodes in Sheep,C.Y.Lee,K.A.Munyard,K.Gregg,J.D.Wetherall,M.J.Stear,andD.M.Groth Volume 2011, Article ID 101848, 11 pages Energetic Cost of Ichthyophonus Infection in Juvenile Pacific Herring (Clupea pallasii), Johanna J. Vollenweider, Jake L. Gregg, Ron A. Heintz, and Paul K. Hershberger Volume 2011, Article ID 926812, 10 pages Helminth Parasites and the Modulation of Joint Inflammation, Chelsea E. Matisz, Jason J. McDougall, Keith A. Sharkey, and Derek M. McKay Volume 2011, Article ID 942616, 8 pages Effects of Environmental Temperature on the Dynamics of Ichthyophoniasis in Juvenile Pacific Herring (Clupea pallasii), Jake L. Gregg, Johanna J. Vollenweider, Courtney A. Grady, Ron A. Heintz, and Paul K. Hershberger Volume 2011, Article ID 563412, 9 pages Possible Roles of Ectophosphatases in Host-Parasite Interactions, Marta T. Gomes, Angela H. Lopes, and JoseRobertoMeyer-Fernandes´ Volume 2011, Article ID 479146, 7 pages Acute Disruption of Bone Marrow B Lymphopoiesis and Apoptosis of Transitional and Marginal Zone B CellsintheSpleenfollowingaBlood-StagePlasmodium chabaudi Infection in Mice, Viki Bockstal, Nathalie Geurts, and Stefan Magez Volume 2011, Article ID 534697, 11 pages An ELISA to Detect Serum Antibodies to the Salivary Gland Toxin of Ixodes holocyclus Neumann in Dogs and Rodents,S.Hall-Mendelin,P.O’Donoghue,R.B.Atwell,R.Lee,andR.A.Hall Volume 2011, Article ID 283416, 6 pages Liver Metabolic Alterations and Changes in Host Intercompartmental Metabolic Correlation during Progression of Malaria, Arjun Sengupta, Angika Basant, Soumita Ghosh, Shobhona Sharma, and Haripalsingh M. Sonawat Volume 2011, Article ID 901854, 14 pages Angiostrongylus vasorum: Experimental Infection and Larval Development in Omalonyx matheroni, L. R. Mozzer, L. C. Montresor, T. H. D. A. Vidigal, and W. S. Lima Volume 2011, Article ID 178748, 4 pages A Dog with Pseudo-Addison Disease Associated with Trichuris vulpis Infection,LuigiVenco, Valentina Valenti, Marco Genchi, and Giulio Grandi Volume 2011, Article ID 682039, 3 pages Excretory-Secretory Products from Hookworm L3 and Adult Worms Suppress Proinflammatory Cytokines in Infected Individuals, Stefan Michael Geiger, Ricardo Toshio Fujiwara, Paula Albuquerque Freitas, Cristiano Lara Massara, Omar dos Santos Carvalho, Rodrigo Correa-Oliveira,ˆ and Jeffrey Michael Bethony Volume 2011, Article ID 512154, 8 pages Parasites or Cohabitants: Cruel Omnipresent Usurpers or Creative “Eminences´ Grises”?, Marcos A. Vannier-Santos and Henrique L. Lenzi Volume 2011, Article ID 214174, 19 pages Hindawi Publishing Corporation Journal of Parasitology Research Volume 2011, Article ID 926706, 10 pages doi:10.1155/2011/926706 Review Article A Sequential Model of Host Cell Killing and Phagocytosis by Entamoeba histolytica Adam Sateriale1, 2 and Christopher D. Huston1, 3 1 Department of Medicine, College of Medicine, The University of Vermont, Room 320 Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405, USA 2 Cell and Molecular Biology Graduate Program, College of Medicine, The University of Vermont, Burlington, VT 05405, USA 3 Department of Microbiology and Molecular Genetics, College of Medicine, The University of Vermont, Room 320 Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405, USA Correspondence should be addressed to Christopher D. Huston, [email protected] Received 24 November 2010; Accepted 19 December 2010 Academic Editor: D. S. Lindsay Copyright © 2011 A. Sateriale and C. D. Huston. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The protozoan parasite Entamoeba histolytica is responsible for invasive intestinal and extraintestinal amebiasis. The virulence of Entamoeba histolytica is strongly correlated with the parasite’s capacity to effectively kill and phagocytose host cells. The process by which host cells are killed and phagocytosed follows a sequential model of adherence, cell killing, initiation of phagocytosis, and engulfment. This paper presents recent advances in the cytolytic and phagocytic processes of Entamoeba histolytica in context of the sequential model. 1. Introduction evolution. Host cells may have recognition patterns similar to those of enteric bacteria that the parasite has evolved to Entamoeba histolytica is an enteric parasite that colonizes the identify. Entamoeba histolytica has been shown to preferen- human intestinal lumen and has the capacity to invade tially phagocytose cells coated with collectins, C-type lectins the epithelium. Although 90% of amebic infections are involved in recognition of ligands that are common to both asymptomatic and self-limiting, there are an estimated 50 bacteria and apoptotic cells [4]. An effective hijacking of the million cases of invasive infection annually [1, 2]. According host’s own innate immune system to increase phagocytosis to the WHO, Entamoeba histolytica is ranked third as a may have led to an invasive phenotype. In further support cause of death among parasites with 100,000 estimated of this theory, Ghosh and Samuelson [3] have shown that deaths annually [1]. The morbidity and mortality of this several signaling proteins required for Entamoeba histolytica’s parasite is primarily seen in developing countries. Ingestion virulence are also utilized to kill and phagocytose bacteria. of contaminated food or water containing infectious cysts Another seemingly plausible explanation is that Entamoeba leads to excystation in the intestine. Each cyst produces histolytica’s invasive phenotype arose in response to host eight motile trophozoites, which colonize the host’s colon. defense mechanisms [5]. Directed apoptosis and subsequent In those cases where the infection is not self limiting, amebic phagocytosis may serve to limit host inflammatory mech- dysentery and liver abscess formation can occur [2]. anisms by suppressing necrosis and subsequent Th1-type The process of invasion and hepatic abscess formation immunity [6]. Cysteine proteases that are known to degrade has no apparent advantage for Entamoeba histolytica [3]. host extracellular matrix also protect Entamoeba histolytica The logical question would then be why did this organ- from complement, secretory IgA, and serum IgG [7–9]. ism evolve to be a pathogen and not a commensal like While the evolutionary basis behind virulence is uncer- its noninvasive cousin, Entamoeba dispar? One theory of tain, the mechanism behind virulence is slowly becom- Entamoeba histolytica’s origin of virulence is coincidental ing clearer. Invasion by Entamoeba histolytica is strongly 2 Journal of Parasitology Research correlated with the parasite’s capacity to kill and phagocy- Many of the proteins recently implicated in adherence tose host cells [10–13].Thefunctionofthisreviewisto have arisen from genomic and transcriptomic analyses of highlight some of the recent advances in understanding the Entamoeba histolytica and nonvirulent Entamoeba. Sequenc- mechanism of cell killing and phagocytosis, and to place ing of the Entamoeba histolytica genome has led to many new these findings in the context of previous knowledge. For the discoveries, truly advancing the field of Entamoeba research purpose of this review, cell killing and phagocytosis have in a manner not seen since Diamond et al. first axenically been organized in a sequential model involving (i) adherence cultured the parasite [27–29]. One such discovery is STIRP to the host cell surface, (ii) contact-dependent cell killing, (serine-threonine-isoleucine rich protein), a protein family (iii) initiation of phagocytosis, and (iv) engulfment (see exclusively expressed in virulent strains of Entamoeba, in Figure 1). vitro. shRNA-mediated silencing of the STIRP family led to a 35% decrease in adhesion to host cells and a subsequent 2. Adherence reduction in cytotoxicity [30]. ROM1 is a serine