Special Issue "Host-Parasite Interactions"

Guest Editor
Prof. Dr. Kris Chadee
Gastrointestinal Research Group, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada
Website: http://www.ucalgary.ca/girg/membership/chadeek
E-Mail: kchadee@ucalgary.ca
Phone: +1 403 210 3975
Interests: Entamoeba histolytica; host-pathogen interaction in the gut; gut innate immunity; inflammation; mucosal immunology; pathogenesis and host defense; pro-inflammatory cytokines

Dear Colleagues,

With the resurgent of diseases that cause immunodeficiency coupled with a rapid rise in drug resistance to a variety of infectious diseases, parasitic infections are emerging and reemerging as a major problem to public health worldwide. Recent advances in host-parasite relationships have unraveled new concepts in parasite pathogenic mechanisms, host innate and immune responses and improved treatment strategies to control and/or limit infection. In this special issue, we invite investigators to submit manuscripts that address the broad diversity of parasitic problems (protozoan and helminths) related to public health issues, pathogenesis, immune responses and host defense mechanisms and emerging treatment strategies to combat parasitic infections.
We look forward to your contribution.

Prof. Dr. Kris Chadee
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

• parasite
• host defense
• vaccine
• pathogenesis
• immunoregulation
• protoza
• helminths
• innate immunity
• inflammation

Type of Paper: Reveiw
Title: The significance of Matrix Metalloproteinases in parasitic infections
Author: Fabrizio Bruschi
Affiliation: Department of Experimental Pathology, Università di Pisa, Via Roma, 55 56122 Pisa, Italy; E-Mail: fabrizio.bruschi@med.unipi.it
Abstract: Matrix metalloproteinases (MMPs) represent a large family of over twenty different secreted or membrane-bound endopeptidases, involved in many physiological (embryogenesis, precursor or stem cell mobilization, tissue remodelling during wound healing, etc.) as well as pathological (inflammation, tumor progression and metastasis in cancer, vascular pathology, etc.) conditions. For long time, MMPs were considered only for the ability to degrade extracellular matrix (ECM) molecules (e.g. collagen, laminin, fibronectin) and to release hidden epitopes from the ECM. In the last years, it has been fully elucidated that these molecules have many other functions, mainly related to the immune response, in consideration of their effects on cytokines, hormones and chemokines. Among others, MMP-2 and MMP-9 are endopeptidases of the MMP family produced by neutrophils, macrophages and monocytes. When infection is associated with leukocyte influx into specific organs, immunopathology and collateral tissue damage may occur. In this review, the involvement of MMPs and in particular of gelatinases in both protozoan and helminth infections will be described. In cerebral malaria, for example, MMPs play a role in the pathogenesis of such disease. Furthermore, also in helminth infections like neurocysticercosis, these enzymes seem to have a pathogenetic significance, due to their disruptive/proteolytic action on blood brain barrier.

Type of Paper: Review
Title: Immune evasion, immunopathology and the regulation of the immune system
Authors: Gabriele Sorci *, Stéphane Cornet, Bruno Faivre
Affiliation: Université de Bourgogne, Unité Mixte de Recherche, Centre national de la recherche scientifique, Dijon, France; E-mail: gabriele.sorci@u-bourgogne.fr (G.S.)
Abstract: Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favour individuals with the most effective immune defences. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defences. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance but also protect from autoimmune diseases. In the last decades the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths) that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favour the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

Type of Paper: Review
Title: Goblet Cell and Mucins: Role in Innate Defense in Enteric Infections
Author: Janice J. Kim^1,2 and Waliul I. Khan^1,2
Affiliation: ¹ Department Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
² Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; E-Mail: khanwal@mcmaster.ca (W.I.K.)
Abstract: Goblet cells reside throughout the gastrointestinal (GI) tract and are responsible for the production and preservation of protective mucus blanket by synthesizing and secreting high molecular weight glycoproteins known as mucins. The concept of the mucus layer functioning as a dynamic protective barrier is suggested by studies showing changes in mucins in inflammatory conditions of the GI tract, by the altered goblet cell response in germ-free animals, and by the enhanced mucus secretion seen in response to infections. The mucin containing mucus layer coating the GI epithelium is the front line of innate host defense. Mucins are likely to be the first molecules that invading pathogens interact with at the cell surface and thus, mucins can limit pathogen binding to other glycoproteins and neutralize the pathogen. This review will focus on what is known on goblet cell response in various GI infections and the regulatory networks that mediate goblet cell function and mucin production in response to intestinal insults. In addition, we describe the current knowledge on the role of mucins in intestinal innate defense. It is the aim of this review to provide the readers with an update on goblet cell biology and current understanding on the role of mucins in host defense in enteric infections.

Type of Paper: Review
Title: Molecular Strategies of Intracellular Parasites for Self-Preservation by Preventing Premature Death of Their Host Cells: The Leishmania Model
Author: Kwang Poo Chang
Affiliation: Department of Microbiology/Immunology, Chicago Medical School, RFUMS, North Chicago, IL 60064, USA; E-Mail: kwangpoo.chang@rosalindfraklin.edu
Abstract: Most obligate intracellular pathogens are vulnerable to attacks by multifarious arrays of lytic factors in the mammalian body fluids. It is advantageous for such pathogens to evolve molecular mechanisms that help them stay in the host cells as the favorable habitat by lengthening their longevity. A unique model to study this is Leishmnia, trypanosomatid protozoa, which parasitize the phagolysosomes of macrophages – the arch-type of phagocytes, which ingest and digest other pathogens. Leishmania infection of macrophages is often seen to overload these host cells, both in experimental and clinical settings, reaching several hundreds of amastigotes per cell. Multiple mechanisms may contribute to this phenomenon. Leishmania has been reported to inhibit the signal pathway of macrophages for apoptosis. These parasites also possess ecto- phosphatases, -kinases and –hydrolases, as well as release these and nucleotide-binding/modifying enzymes, e.g., nucleoside diphosphate kinases. Modifications of host cells and their released mediators are expected to play significant roles, accounting for the leishmanial ability to preserve the integrity of the infected macrophages. It is envisioned from such Leishmania activities that the heavily loaded macrophages may degenerate instead of cytolysis, sending signals to attract non-infected macrophages. These freshly arrived macrophages gang together to phagocytose the moribund and heavily infected cells via “scavenging phagocytosis”, thereby acquiring Leishmania. Metastasis of infection this way is expected to benefit the pathogens by avoiding their unwanted exposure to the hostile milieu outside of the host cells.

Type of Paper: Article
Title: Use of a Th1 Stimulator Adjuvant for Vaccination Against Neospora caninum Infection in the Pregnant Mouse Model
Author: Thierry Monney^1*, Denis Grandgirard², Stephen L. Leib², Andrew Hemphill^1*
Affiliation: ¹Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland; ²Institute for Infectious Diseases, University of Berne, Friedbühlstrasse 51, CH-3010 Berne, Switzerland; E-Mail: andrew.hemphill@vetsuisse.unibe.ch (A.H.)
Abstract: Vertical transmission from an infected cow to its fetus accounts for the vast majority of new Neospora caninum infections in cattle. A vaccine composed of a chimeric antigen named recNcMIC3-1-R, based on predicted immunogenic epitopes (domains?) of the two microneme proteins NcMIC1 and NcMIC3, the rhopty protein NcROP2, and emulsified in saponin adjuvants, significantly reduced the cerebral infection in non-pregnant BALB/c mice. Protection was associated with a mixed Th1/Th2-type cytokine response. However, the same vaccine formulation elicited a Th2-type immune response in pregnant mice and did not prevent vertical transmission or disease, neither in dams nor in offspring mice. In this study, an alternative vaccine formulation containing recNcMIC3-1-R emulsified in Freund’s incomplete adjuvant, a stimulator of the cellular immunity, was investigated. No protection against vertical transmission and cerebral infection in the pregnant mice and a very limited protective effect in the non-pregnant mice were observed. The vaccine induced a Th1-type immune response characterized by high IgG2a titres and strong IFN-γ expression, which appeared detrimental to pregnancy. These results demonstrate the necessity, but also the difficulty, of acquiring a suitable Th1/Th2 balance in order to achieve protection by vaccination with recombinant antigens in the pregnant mouse model.