Pathogens

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Open AccessReview

Antimicrobial Human β-Defensins in the Colon and Their Role in Infectious and Non-Infectious Diseases

by Eduardo R. Cobo and Kris Chadee

Pathogens 2013, 2(1), 177-192; https://doi.org/10.3390/pathogens2010177 - 19 Mar 2013

Cited by 56 | Viewed by 10184

β-defensins are small cationic antimicrobial peptides secreted by diverse cell types including colonic epithelial cells. Human β-defensins form an essential component of the intestinal lumen in innate immunity. The defensive mechanisms of β-defensins include binding to negatively charged microbial membranes that cause cell [...] Read more.

β-defensins are small cationic antimicrobial peptides secreted by diverse cell types including colonic epithelial cells. Human β-defensins form an essential component of the intestinal lumen in innate immunity. The defensive mechanisms of β-defensins include binding to negatively charged microbial membranes that cause cell death and chemoattraction of immune cells. The antimicrobial activity of β-defensin is well reported in vitro against several enteric pathogens and in non-infectious processes such as inflammatory bowel diseases, which alters β-defensin production. However, the role of β-defensin in vivo in its interaction with other immune components in host defense against bacteria, viruses and parasites with more complex membranes is still not well known. This review focuses on the latest findings regarding the role of β-defensin in relevant human infectious and non-infectious diseases of the colonic mucosa. In addition, we summarize the most significant aspects of β-defensin and its antimicrobial role in a variety of disease processes. Full article

(This article belongs to the Special Issue Host-Parasite Interactions)

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Open AccessReview

Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases

by Shigeyoshi Fujiwara, Go Matsuda and Ken-Ichi Imadome

Pathogens 2013, 2(1), 153-176; https://doi.org/10.3390/pathogens2010153 - 14 Mar 2013

Cited by 17 | Viewed by 8396

Abstract

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including [...] Read more.

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus. Full article

(This article belongs to the Special Issue Pathogen Infection Models)

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Open AccessArticle

Order of Inoculation during Heligmosomoides bakeri and Hymenolepis microstoma Coinfection Alters Parasite Life History and Host Responses

by Paul R. Clark, W. Timothy Ward, Samantha A. Lang, Alaa Saghbini and Deborah M. Kristan

Pathogens 2013, 2(1), 130-152; https://doi.org/10.3390/pathogens2010130 - 01 Mar 2013

Cited by 5 | Viewed by 6778

Abstract

Parasite life history may differ during coinfection compared to single infections, and the order of infection may be an important predictor of life history traits. We subjected laboratory mice (Mus musculus) to single and coinfections with Heligmosomoides bakeri and Hymenolepis microstoma [...] Read more.

Parasite life history may differ during coinfection compared to single infections, and the order of infection may be an important predictor of life history traits. We subjected laboratory mice (Mus musculus) to single and coinfections with Heligmosomoides bakeri and Hymenolepis microstoma and measured life history traits of worms and also hepatobiliary and morphological responses by the host. We found that fewer H. bakeri larvae established, and adult worms were shorter and produced fewer eggs during a coinfection where H. microstoma occurred first. H. microstoma grew more and released more eggs after simultaneous inoculation of both parasites compared to a single H. microstoma infection, despite similar worm numbers. Mouse small intestine mass, but not length, varied with coinfection and bile duct mass was largest when H. microstoma was given alone or first. Mouse serum alkaline phosphatase levels were greatest for mice infected with H. microstoma only but did not vary with number of scolices; no change in mouse serum alanine transaminase levels was observed. Overall, the order of coinfection influenced life history traits of both H. bakeri and H. microstoma, but changes in survival, growth, and reproduction with order of inoculation were not consistent between the two parasites. Full article

(This article belongs to the Special Issue Host-Parasite Interactions)

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Open AccessReview

The Significance of Matrix Metalloproteinases in Parasitic Infections Involving the Central Nervous System

by Fabrizio Bruschi and Barbara Pinto

Pathogens 2013, 2(1), 105-129; https://doi.org/10.3390/pathogens2010105 - 19 Feb 2013

Cited by 38 | Viewed by 11446

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 remodeling during wound healing, etc.), as well as pathological (inflammation, tumor progression and metastasis in cancer, [...] Read more.

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 remodeling during wound healing, etc.), as well as pathological (inflammation, tumor progression and metastasis in cancer, vascular pathology, etc.) conditions. For a 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 few 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 diseases. Also, trypanosomosis and toxoplasmosis will be considered for protozoan infections, as well as neurocysticercosis and angiostrongyloidosis, as regards helminthiases. All these situations have in common the proteolytic action on the blood brain barrier, mediated by MMPs. Full article

(This article belongs to the Special Issue Host-Parasite Interactions)

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Open AccessArticle

Heterogeneity of the Abnormal Prion Protein (PrP^Sc) of the Chandler Scrapie Strain

by Kazuo Kasai, Yoshifumi Iwamaru, Kentaro Masujin, Morikazu Imamura, Shirou Mohri and Takashi Yokoyama

Pathogens 2013, 2(1), 92-104; https://doi.org/10.3390/pathogens2010092 - 18 Feb 2013

Cited by 1 | Viewed by 6120

Abstract

The pathological prion protein, PrP^Sc, displays various sizes of aggregates. In this study, we investigated the conformation, aggregation stability and proteinase K (PK)-sensitivity of small and large PrP^Sc aggregates of mouse-adapted prion strains. We showed that small PrP^Sc aggregates, [...] Read more.

The pathological prion protein, PrP^Sc, displays various sizes of aggregates. In this study, we investigated the conformation, aggregation stability and proteinase K (PK)-sensitivity of small and large PrP^Sc aggregates of mouse-adapted prion strains. We showed that small PrP^Sc aggregates, previously thought to be PK-sensitive, are resistant to PK digestion. Furthermore, we showed that small PrP^Sc aggregates of the Chandler scrapie strain have greater resistance to PK digestion and aggregation-denaturation than large PrP^Sc aggregates of this strain. We conclude that this strain consists of heterogeneous PrP^Sc. Full article

(This article belongs to the Special Issue Prions)

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Open AccessReview

Immune Evasion, Immunopathology and the Regulation of the Immune System

by Gabriele Sorci, Stéphane Cornet and Bruno Faivre

Pathogens 2013, 2(1), 71-91; https://doi.org/10.3390/pathogens2010071 - 13 Feb 2013

Cited by 33 | Viewed by 10997

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 favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of [...] Read more.

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 favor individuals with the most effective immune defenses. 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 defenses. 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 favor 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. Full article

(This article belongs to the Special Issue Host-Parasite Interactions)

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Open AccessReview

Goblet Cells and Mucins: Role in Innate Defense in Enteric Infections

by Janice J. Kim and Waliul I. Khan

Pathogens 2013, 2(1), 55-70; https://doi.org/10.3390/pathogens2010055 - 04 Feb 2013

Cited by 191 | Viewed by 24980

Abstract

Goblet cells reside throughout the gastrointestinal (GI) tract and are responsible for the production and preservation of a 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 [...] Read more.

Goblet cells reside throughout the gastrointestinal (GI) tract and are responsible for the production and preservation of a 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, can limit binding to other glycoproteins and neutralize the pathogen. This review will focus on what is known about 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. Full article

(This article belongs to the Special Issue Host-Parasite Interactions)

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Open AccessReview

Targeting Plasmodium falciparum Hsp90: Towards Reversing Antimalarial Resistance

by Dea Shahinas, Asongna Folefoc and Dylan R. Pillai

Pathogens 2013, 2(1), 33-54; https://doi.org/10.3390/pathogens2010033 - 04 Feb 2013

Cited by 35 | Viewed by 14054

Abstract

Malaria continues to exact a great human toll in tropical settings. Antimalarial resistance is rife and the parasite inexorably develops mechanisms to outwit our best drugs, including the now first-line choice, artesunate. Novel strategies to circumvent resistance are needed. Here we detail drug [...] Read more.

Malaria continues to exact a great human toll in tropical settings. Antimalarial resistance is rife and the parasite inexorably develops mechanisms to outwit our best drugs, including the now first-line choice, artesunate. Novel strategies to circumvent resistance are needed. Here we detail drug development focusing on heat shock protein 90 and its central role as a chaperone. A growing body of evidence supports the role for Hsp90 inhibitors as adjunctive drugs able to restore susceptibility to traditionally efficacious compounds like chloroquine. Full article

(This article belongs to the Special Issue Host-Parasite Interactions)

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1446 KiB

Open AccessArticle

Defensin Production by Human Limbo-Corneal Fibroblasts Infected with Mycobacteria

by Jorge I. Castañeda-Sánchez, Blanca E. García-Pérez, Ana R. Muñoz-Duarte, Shantal L. Baltierra-Uribe, Herlinda Mejia-López, Carlos López-López, Victor M. Bautista-De Lucio, Atzín Robles-Contreras and Julieta Luna-Herrera

Pathogens 2013, 2(1), 13-32; https://doi.org/10.3390/pathogens2010013 - 04 Feb 2013

Cited by 23 | Viewed by 7891

Abstract

Epithelial cells of the cornea and the conjunctiva constitutively produce antimicrobial peptides; however, the production of defensins by other cell types located around the eye has not been investigated. We analyzed the production of beta-defensins (hBD) and cathelicidin LL-37 during the infection of [...] Read more.

Epithelial cells of the cornea and the conjunctiva constitutively produce antimicrobial peptides; however, the production of defensins by other cell types located around the eye has not been investigated. We analyzed the production of beta-defensins (hBD) and cathelicidin LL-37 during the infection of primary limbo-corneal fibroblasts with M. tuberculosis (MTB), M. abscessus (MAB), and M. smegmatis (MSM). The intracellular survival of each mycobacterium, the production of cytokines and the changes on the distribution of the actin filaments during the infection were also analyzed. Fibroblasts produce basal levels of hBD1 and LL-37 and under PMA stimulation they produce hBD2, hBD3 and overexpress hBD1 and LL-37. MAB induced the highest levels of hBD1 and LL-37 and intermediate levels of IL-6; however, MAB was not eliminated. In addition, MAB induced the greatest change to the distribution of the actin filaments. MTB also produced changes in the structure of the cytoskeleton and induced low levels of hBD1 and IL-6, and intermediate levels of LL-37. The balance of these molecules induced by MTB appeared to contribute to the non-replicative state observed in the limbo-corneal cells. MSM induced the lowest levels of hBD1 and LL-37 but the highest levels of IL-6; MSM was eliminated. The results suggest that mycobacterial infections regulate the production of antimicrobial peptides and cytokines, which in conjunction can contribute to the control of the bacilli. Full article

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183 KiB

Open AccessReview

Human Bocavirus: Lessons Learned to Date

by Oliver Schildgen

Pathogens 2013, 2(1), 1-12; https://doi.org/10.3390/pathogens2010001 - 11 Jan 2013

Cited by 50 | Viewed by 7283

Abstract

Human bocavirus (HBoV) was identified as the second human parvovirus with pathogenic potential in 2005 in respiratory samples from children suffering from viral respiratory infections of unknown etiology. Since its first description, a large number of clinical studies have been performed that address [...] Read more.

Human bocavirus (HBoV) was identified as the second human parvovirus with pathogenic potential in 2005 in respiratory samples from children suffering from viral respiratory infections of unknown etiology. Since its first description, a large number of clinical studies have been performed that address the clinical significance of HBoV detection and the molecular biology of the virus. This review summarizes the most important steps taken in HBoV research to date and addresses open questions that need to be answered in the future to provide a better understanding of the role of a virus that is difficult to grow in cell culture and is suspected to be a pathogen, although it has not yet fulfilled Koch’s postulates. Full article

(This article belongs to the Special Issue Pathogen Infection Models)

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Pathogens, Volume 2, Issue 1 (March 2013) – 10 articles , Pages 1-192

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