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Pathogens
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Biology of Parasitism
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Biology of Parasitism

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 27515

Special Issue Editors

Dr. Samarchith P. Kurup

E-Mail Website
Guest Editor
Center for Tropical and Emerging Global Diseases, Department of Cellular Biology, University of Georgia, Athens, GA, USA
Interests: immunoparasitology
Dr. Rahul Vijay

E-Mail Website
Guest Editor
Center for Cancer Biology Immunology and Infection, Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
Interests: Immunoparasitology; Immunomodulation

Special Issue Information

Dear Colleagues,

Parasites are highly diverse and complex organisms which have evolved to successfully infect other eukaryotic hosts. Over centuries they have remained among the most infectious of pathogens affecting the animal kingdom, including humans. Understanding the nature of host–parasite interaction has been paramount to combating parasitic diseases, and has taught us a great deal about eukaryotic biology in all its breadth and diversity. Through this Special Issue of Pathogens, we hope to bring together outstanding researchers to contribute primary research and/or review articles that create a symphony of scientific expeditions into the world of eukaryotic parasite biology. We aim to showcase why parasites are such unique and intriguing creations of nature, and why we should continue to study them. 

To attract the interest and intrigue of a wider readership we would like to invite investigators working on any pathogenic parasites (within the broader areas covering their ecology, genetics, genomics, immunology, detection, public health, and vaccine development) to submit their manuscripts in the form of original research articles and reviews.

Sincerely,

Dr. Samarchith P. Kurup
Dr. Rahul Vijay
Guest Editors

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind 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 monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Malaria
  • Leishmania
  • Toxoplasma
  • Trypanosoma
  • Parasites
  • Biology
  • Infection
  • Eukaryotic

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Published Papers (10 papers)

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Research

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10 pages, 1035 KiB  
Article
Plasmodium Infection–Cure Cycles Increase the Capacity of Phagocytosis in Conventional Dendritic Cells
by Ryosuke Adachi and Takahiko Tamura
Pathogens 2023, 12(10), 1262; https://doi.org/10.3390/pathogens12101262 - 19 Oct 2023
Viewed by 1157
Abstract
Malaria stands as one of the most pervasive human infectious diseases globally and represents a prominent cause of mortality. Immunity against clinical malaria disease is achieved through multiple infection and treatment cycles, culminating in a substantial reduction in parasite burden. To investigate this [...] Read more.
Malaria stands as one of the most pervasive human infectious diseases globally and represents a prominent cause of mortality. Immunity against clinical malaria disease is achieved through multiple infection and treatment cycles, culminating in a substantial reduction in parasite burden. To investigate this phenomenon, we established a murine model involving repeated infection–cure cycles, whereby mice were infected with the lethal rodent malarial parasite Plasmodium berghei ANKA and subsequently treated with the anti-malarial drug pyrimethamine. Our earlier study revealed a significant decrease in the capacity of conventional dendritic cells (cDCs) to produce cytokines upon stimulation in infection-cured mice. In the present study, we aimed to further elucidate the modulation of cDC functionality during repeated infection–cure cycles by examining their phagocytic capacity. Administering fluorescent beads to mice resulted in no significant difference in the total number of bead-positive cells within the spleens of both uninfected and 3-cure (three cycles of infection–cure) mice. However, the proportion of the CD11c+F4/80− population within bead-positive cells was notably higher in 3-cure mice compared to uninfected mice. Subsequent in vitro analysis of bead phagocytosis by purified CD11c+cDCs revealed that the cDC2 subset from 3-cure mice exhibited significantly enhanced phagocytic capacity in comparison to their uninfected counterparts. These findings underscore the substantial impact of repeated infection–cure cycles on various facets of cDC function, potentially influencing the trajectory of immune responses against subsequent malaria infections. Full article
(This article belongs to the Special Issue Biology of Parasitism)
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10 pages, 1108 KiB  
Article
The Occurrence of Cryptosporidium spp. in Wild-Living Carnivores in Poland—A Question Concerning Its Host Specificity
by Agnieszka Perec-Matysiak, Joanna Hildebrand, Marcin Popiołek and Katarzyna Buńkowska-Gawlik
Pathogens 2023, 12(2), 198; https://doi.org/10.3390/pathogens12020198 - 28 Jan 2023
Cited by 7 | Viewed by 2576
Abstract
Cryptosporidium is an apicomplexan protozoan parasite that primarily infects the gastrointestinal epithelium in humans and domestic and wild animals. The majority of studies have been focused on human, livestock, and pet infections. Hence, Cryptosporidium spp. in wildlife, including wild carnivores, remained neglected. There [...] Read more.
Cryptosporidium is an apicomplexan protozoan parasite that primarily infects the gastrointestinal epithelium in humans and domestic and wild animals. The majority of studies have been focused on human, livestock, and pet infections. Hence, Cryptosporidium spp. in wildlife, including wild carnivores, remained neglected. There are several studies reporting the occurrence of Cryptosporidium spp. in wild foxes, but these are only a few molecular surveys; no data is available concerning the occurrence of this parasite in raccoon dogs and martens in Europe, and to the best of our knowledge to date, only one study has reported Cryptosporidium from badgers in Spain. Therefore, we used molecular analyses to identify and genotype Cryptosporidium spp. in wild-living mesocarnivores in Poland. A total of 322 individual fecal samples from six carnivore species, i.e., raccoon, raccoon dog, red fox, European badger, pine, and beech martens were collected and then analyzed for the presence of Cryptosporidium spp. using the nested PCR method. The appearance of PCR products in the reaction with Cryptosporidium-specific primers against the 18S rRNA and actin genes demonstrated that Cryptosporidium spp. occurred in 23.0% of all examined species of animals. Performed sequence analyses showed the presence of the Cryptosporidium skunk genotype, Cryptosporidium vole genotype II, Cryptosporidium canis dog and fox genotypes, as well as Cryptosporidium erinacei, Cryptosporidium ditrichi, Cryptosporidium suis, and Cryptosporidium alticolis, in these hosts. Molecular data presented here indicate that examined mesocarnivores may be a significant reservoir of specific and non-specific Cryptosporidium species, including those with zoonotic potential. Most studies of carnivores have described the presence of non-specific Cryptosporidium spp. in carnivore hosts, and this is probably the result of the transfer of these parasites from prey species through the digestive tract or the transfer of the parasite from a contaminated environment. Full article
(This article belongs to the Special Issue Biology of Parasitism)
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13 pages, 2041 KiB  
Article
Cryopreservation of Plasmodium Sporozoites
by Carson Bowers, Lisa Hancox, Kristen Peissig, Justine C. Shiau, Amélie Vantaux, Benoit Witkowski, Sivchheng Phal, Steven P. Maher, John T. Harty, Dennis E. Kyle and Samarchith P. Kurup
Pathogens 2022, 11(12), 1487; https://doi.org/10.3390/pathogens11121487 - 7 Dec 2022
Cited by 4 | Viewed by 2649
Abstract
Malaria is a deadly disease caused by the parasite, Plasmodium, and impacts the lives of millions of people around the world. Following inoculation into mammalian hosts by infected mosquitoes, the sporozoite stage of Plasmodium undergoes obligate development in the liver before infecting [...] Read more.
Malaria is a deadly disease caused by the parasite, Plasmodium, and impacts the lives of millions of people around the world. Following inoculation into mammalian hosts by infected mosquitoes, the sporozoite stage of Plasmodium undergoes obligate development in the liver before infecting erythrocytes and causing clinical malaria. The most promising vaccine candidates for malaria rely on the use of attenuated live sporozoites to induce protective immune responses. The scope of widespread testing or clinical use of such vaccines is limited by the absence of efficient, reliable, or transparent strategies for the long-term preservation of live sporozoites. Here we outline a method to cryopreserve the sporozoites of various human and murine Plasmodium species. We found that the structural integrity, viability, and in vivo or in vitro infectiousness were conserved in the recovered cryopreserved sporozoites. Cryopreservation using our approach also retained the transgenic properties of sporozoites and immunization with cryopreserved radiation attenuated sporozoites (RAS) elicited strong immune responses. Our work offers a reliable protocol for the long-term storage and recovery of human and murine Plasmodium sporozoites and lays the groundwork for the widespread use of live sporozoites for research and clinical applications. Full article
(This article belongs to the Special Issue Biology of Parasitism)
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14 pages, 2414 KiB  
Article
Kinetoplastid Species Maintained by a Small Mammal Community in the Pantanal Biome
by Filipe Martins Santos, Nayara Yoshie Sano, Sany Caroline Liberal, Maria Augusta Dario, Wesley Arruda Gimenes Nantes, Fernanda Moreira Alves, Alanderson Rodrigues da Silva, Carina Elisei De Oliveira, André Luiz Rodrigues Roque, Heitor Miraglia Herrera and Ana Maria Jansen
Pathogens 2022, 11(10), 1205; https://doi.org/10.3390/pathogens11101205 - 19 Oct 2022
Cited by 4 | Viewed by 2163
Abstract
Kinetoplastids include species economically important in agriculture, livestock, and human health. We evaluated the richness of kinetoplastids that infect small mammals in patches of unflooded forests in the Pantanal biome, an area where we hypothesize that its diversity is higher than currently recognized. [...] Read more.
Kinetoplastids include species economically important in agriculture, livestock, and human health. We evaluated the richness of kinetoplastids that infect small mammals in patches of unflooded forests in the Pantanal biome, an area where we hypothesize that its diversity is higher than currently recognized. Hemocultures (HC) and Next Generation Sequencing (NGS) targeting the 18S rDNA gene were employed for the detection of kinetoplastids. We grouped the positive samples into pools for each small mammal species (Monodelphis domestica, Thylamys macrurus, Oecomys mamorae, Thrichomys fosteri, Clyomys laticeps, and Holochilus chacarius). Eight parasite species were identified: Leishmania amazonensis, L. infantum; Trypanosoma cascavelli (HC + NGS), T. cruzi, T. lainsoni, T. rangeli (HC + NGS), Trypanosoma sp. DID, and Neobodo sp. The use of a tool as sensitive as NGS has increased our awareness of the diversity of kinetoplastids, as well as their host range, with emphasis on the species O. mamorae (seven kinetoplastid species, excepting T. cascavelli in a pool of nine individuals) and T. macrurus (four kinetoplastid species in a single individual). Furthermore, L. infantum and L. amazonensis infections were described in small mammals from this region for the first time. These findings make it mandatory to revisit the kinetoplastids/host associations proposed so far. Full article
(This article belongs to the Special Issue Biology of Parasitism)
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18 pages, 1997 KiB  
Article
Polymorphic Molecular Signatures in Variable Regions of the Plasmodium falciparum var2csa DBL3x Domain Are Associated with Virulence in Placental Malaria
by Eldin Talundzic, Stephen Scott, Simon O. Owino, David S. Campo, Naomi W. Lucchi, Venkatachalam Udhayakumar, Julie M. Moore and David S. Peterson
Pathogens 2022, 11(5), 520; https://doi.org/10.3390/pathogens11050520 - 28 Apr 2022
Cited by 3 | Viewed by 2428
Abstract
The Plasmodium falciparum protein VAR2CSA allows infected erythrocytes to accumulate within the placenta, inducing pathology and poor birth outcomes. Multiple exposures to placental malaria (PM) induce partial immunity against VAR2CSA, making it a promising vaccine candidate. However, the extent to which VAR2CSA genetic [...] Read more.
The Plasmodium falciparum protein VAR2CSA allows infected erythrocytes to accumulate within the placenta, inducing pathology and poor birth outcomes. Multiple exposures to placental malaria (PM) induce partial immunity against VAR2CSA, making it a promising vaccine candidate. However, the extent to which VAR2CSA genetic diversity contributes to immune evasion and virulence remains poorly understood. The deep sequencing of the var2csa DBL3X domain in placental blood from forty-nine primigravid and multigravid women living in malaria-endemic western Kenya revealed numerous unique sequences within individuals in association with chronic PM but not gravidity. Additional analysis unveiled four distinct sequence types that were variably present in mixed proportions amongst the study population. An analysis of the abundance of each of these sequence types revealed that one was inversely related to infant gestational age, another was inversely related to placental parasitemia, and a third was associated with chronic PM. The categorization of women according to the type to which their dominant sequence belonged resulted in the segregation of types as a function of gravidity: two types predominated in multigravidae whereas the other two predominated in primigravidae. The univariate logistic regression analysis of sequence type dominance further revealed that gravidity, maternal age, placental parasitemia, and hemozoin burden (within maternal leukocytes), reported a lack of antimalarial drug use, and infant gestational age and birth weight influenced the odds of membership in one or more of these sequence predominance groups. Cumulatively, these results show that unique var2csa sequences differentially appear in women with different PM exposure histories and segregate to types independently associated with maternal factors, infection parameters, and birth outcomes. The association of some var2csa sequence types with indicators of pathogenesis should motivate vaccine efforts to further identify and target VAR2CSA epitopes associated with maternal morbidity and poor birth outcomes. Full article
(This article belongs to the Special Issue Biology of Parasitism)
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9 pages, 239 KiB  
Article
Parasitic Infections in Internationally Adopted Children: A Twelve-Year Retrospective Study
by Elena Chiappini, Teresa Paba, Matilde Bestetti and Luisa Galli
Pathogens 2022, 11(3), 354; https://doi.org/10.3390/pathogens11030354 - 15 Mar 2022
Cited by 2 | Viewed by 2484
Abstract
Parasitic infections (PIs) are among the most frequent infectious diseases globally. Previous studies reported discrepant results regarding the prevalence of PIs in internationally adopted children (IAC). Data from IAC referred to our paediatric university hospital in 2009–2021 were collected to evaluate the frequency [...] Read more.
Parasitic infections (PIs) are among the most frequent infectious diseases globally. Previous studies reported discrepant results regarding the prevalence of PIs in internationally adopted children (IAC). Data from IAC referred to our paediatric university hospital in 2009–2021 were collected to evaluate the frequency of PIs by the use of stool microscopic examination, antigen assays for Giardia lamblia and Cryptosporidium parvum, and serological tests for Toxocara canis, Strongyloides stercoralis, Schistosoma mansoni, Echinococcus spp., Taenia solium, and Trypanosoma cruzi. Uni- and multivariate logistic regression analyses were performed to evaluate risk factors for PIs and eosinophilia. The proportion of IAC with at least one positive test was 26.83% (640/2385); 2.13% (n = 51) had positive tests for 2 or 3 parasites. A positive assay for helminthic infection was retrieved in 11.07% of children (n = 264), and 17.86% (n = 426) presented with eosinophilia. The most common positive tests were anti-Toxocara canis antibodies (n = 312; 13.8%), followed by positive stool antigen for Giardia lamblia (n = 290; 12.16%), and positive microscopic stool examination for Blastocystis hominis (n = 76; 3.19%). A statistically significant association was found between PIs and region of origin (children from Latin America and Africa were more likely to present PIs than children from Eastern Europe), age 5–14 years, and eosinophilia. No significant association was observed between PIs and gender, vitamin D deficiency, or anemia. In conclusion, PIs are relevant in IAC and an accurate protocol is needed to evaluate IAC once they arrive in their adoptive country. Full article
(This article belongs to the Special Issue Biology of Parasitism)
18 pages, 2771 KiB  
Article
HIF-α Activation Impacts Macrophage Function during Murine Leishmania major Infection
by Manjunath Bettadapura, Hayden Roys, Anne Bowlin, Gopinath Venugopal, Charity L. Washam, Lucy Fry, Steven Murdock, Humphrey Wanjala, Stephanie D. Byrum and Tiffany Weinkopff
Pathogens 2021, 10(12), 1584; https://doi.org/10.3390/pathogens10121584 - 6 Dec 2021
Cited by 3 | Viewed by 2935
Abstract
Leishmanial skin lesions are characterized by inflammatory hypoxia alongside the activation of hypoxia-inducible factors, HIF-1α and HIF-2α, and subsequent expression of the HIF-α target VEGF-A during Leishmania major infection. However, the factors responsible for HIF-α activation are not known. We hypothesize that hypoxia [...] Read more.
Leishmanial skin lesions are characterized by inflammatory hypoxia alongside the activation of hypoxia-inducible factors, HIF-1α and HIF-2α, and subsequent expression of the HIF-α target VEGF-A during Leishmania major infection. However, the factors responsible for HIF-α activation are not known. We hypothesize that hypoxia and proinflammatory stimuli contribute to HIF-α activation during infection. RNA-Seq of leishmanial lesions revealed that transcripts associated with HIF-1α signaling were induced. To determine whether hypoxia contributes to HIF-α activation, we followed the fate of myeloid cells infiltrating from the blood and into hypoxic lesions. Recruited myeloid cells experienced hypoxia when they entered inflamed lesions, and the length of time in lesions increased their hypoxic signature. To determine whether proinflammatory stimuli in the inflamed tissue can also influence HIF-α activation, we subjected macrophages to various proinflammatory stimuli and measured VEGF-A. While parasites alone did not induce VEGF-A, and proinflammatory stimuli only modestly induced VEGF-A, HIF-α stabilization increased VEGF-A during infection. HIF-α stabilization did not impact parasite entry, growth, or killing. Conversely, the absence of ARNT/HIF-α signaling enhanced parasite internalization. Altogether, these findings suggest that HIF-α is active during infection, and while macrophage HIF-α activation promotes lymphatic remodeling through VEGF-A production, HIF-α activation does not impact parasite internalization or control. Full article
(This article belongs to the Special Issue Biology of Parasitism)
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Review

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14 pages, 1980 KiB  
Review
Role of TAM Receptors in Antimalarial Humoral Immune Response
by Lijo John and Rahul Vijay
Pathogens 2024, 13(4), 298; https://doi.org/10.3390/pathogens13040298 - 2 Apr 2024
Viewed by 1893
Abstract
Immune response against malaria and the clearance of Plasmodium parasite relies on germinal-center-derived B cell responses that are temporally and histologically layered. Despite a well-orchestrated germinal center response, anti-Plasmodium immune response seldom offers sterilizing immunity. Recent studies report that certain pathophysiological features [...] Read more.
Immune response against malaria and the clearance of Plasmodium parasite relies on germinal-center-derived B cell responses that are temporally and histologically layered. Despite a well-orchestrated germinal center response, anti-Plasmodium immune response seldom offers sterilizing immunity. Recent studies report that certain pathophysiological features of malaria such as extensive hemolysis, hypoxia as well as the extrafollicular accumulation of short-lived plasmablasts may contribute to this suboptimal immune response. In this review, we summarize some of those studies and attempt to connect certain host intrinsic features in response to the malarial disease and the resultant gaps in the immune response. Full article
(This article belongs to the Special Issue Biology of Parasitism)
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22 pages, 1348 KiB  
Review
The Tapeworm Hymenolepis diminuta as an Important Model Organism in the Experimental Parasitology of the 21st Century
by Anna Sulima-Celińska, Alicja Kalinowska and Daniel Młocicki
Pathogens 2022, 11(12), 1439; https://doi.org/10.3390/pathogens11121439 - 29 Nov 2022
Cited by 8 | Viewed by 5887
Abstract
The tapeworm Hymenolepis diminuta is a common parasite of the small intestine in rodents but it can also infect humans. Due to its characteristics and ease of maintenance in the laboratory, H. diminuta is also an important model species in studies of cestodiasis, [...] Read more.
The tapeworm Hymenolepis diminuta is a common parasite of the small intestine in rodents but it can also infect humans. Due to its characteristics and ease of maintenance in the laboratory, H. diminuta is also an important model species in studies of cestodiasis, including the search for new drugs, treatments, diagnostics and biochemical processes, as well as its host–parasite interrelationships. A great deal of attention has been devoted to the immune response caused by H. diminuta in the host, and several studies indicate that infection with H. diminuta can reduce the severity of concomitant disease. Here, we present a critical review of the experimental research conducted with the use of H. diminuta as a model organism for over more than two decades (in the 21st century). The present review evaluates the tapeworm H. diminuta as a model organism for studying the molecular biology, biochemistry and immunology aspects of parasitology, as well as certain clinical applications. It also systematizes the latest research on this species. Its findings may contribute to a better understanding of the biology of tapeworms and their adaptation to parasitism, including complex correlations between H. diminuta and invertebrate and vertebrate hosts. It places particular emphasis on its value for the further development of modern experimental parasitology. Full article
(This article belongs to the Special Issue Biology of Parasitism)
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9 pages, 275 KiB  
Review
Temporally Evolving and Context-Dependent Functions of Cytokines That Regulate Murine Anti-Plasmodium Humoral Immunity
by Fionna A. Surette and Noah S. Butler
Pathogens 2022, 11(5), 523; https://doi.org/10.3390/pathogens11050523 - 29 Apr 2022
Cited by 1 | Viewed by 1866
Abstract
Protective immunity against blood-stage Plasmodium infection and the disease malaria depends on antibodies secreted from high-affinity B cells selected during the germinal center (GC) response. The induction and stability of the GC response require the activation and direct cell–cell communication between parasite-specific CD4 [...] Read more.
Protective immunity against blood-stage Plasmodium infection and the disease malaria depends on antibodies secreted from high-affinity B cells selected during the germinal center (GC) response. The induction and stability of the GC response require the activation and direct cell–cell communication between parasite-specific CD4 helper T cells and B cells. However, cytokines secreted by helper T cells, B cells, and multiple other innate and adaptive immune cells also contribute to regulating the magnitude and protective functions of GC-dependent humoral immune responses. Here, we briefly review emerging data supporting the finding that specific cytokines can exhibit temporally distinct and context-dependent influences on the induction and maintenance of antimalarial humoral immunity. Full article
(This article belongs to the Special Issue Biology of Parasitism)
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