Review

Authors: Jianya Peng, Mark C Siracusa

It has been appreciated that basophilia is a common feature of helminth infections for approximately 50 years. The ability of basophils to secrete IL-4 and other type 2 cytokines has supported the prevailing notion that basophils contribute to antihelminth immunity by promoting optimal type 2 T helper (Th2) cell responses. While this appears to be the case in several helminth infections, emerging studies are also revealing that the effector functions of basophils are extremely diverse and parasite-specific. Further, new reports now suggest that basophils can restrict type 2 inflammation in a manner that preserves the integrity of helminth-affected tissue. Finally, exciting data has also demonstrated that basophils can regulate inflammation by participating in neuro-immune interactions. This article will review the current state of basophil biology and describe how recent studies are transforming our understanding of the role basophils play in the context of helminth infections.

Topics: Animals; Basophils; Cytokines; Helminths; Humans; Inflammation; Th2 Cells

PubMed: 34815162
DOI: 10.1016/j.smim.2021.101529

Review

Authors: Diana Cortes-Selva, Keke Fairfax

Macrophages are fundamental to sustain physiological equilibrium and to regulate the pathogenesis of parasitic and metabolic processes. The functional heterogeneity and immune responses of macrophages are shaped by cellular metabolism in response to the host's intrinsic factors, environmental cues and other stimuli during disease. Parasite infections induce a complex cascade of cytokines and metabolites that profoundly remodel the metabolic status of macrophages. In particular, helminths polarize macrophages to an M2 state and induce a metabolic shift towards reliance on oxidative phosphorylation, lipid oxidation and amino acid metabolism. Accumulating data indicate that helminth-induced activation and metabolic reprogramming of macrophages underlie improvement in overall whole-body metabolism, denoted by improved insulin sensitivity, body mass in response to high-fat diet and atherogenic index in mammals. This review aims to highlight the metabolic changes that occur in human and murine-derived macrophages in response to helminth infections and helminth products, with particular interest in schistosomiasis and soil-transmitted helminths.

Topics: Animals; Cytokines; Helminthiasis; Helminths; Humans; Intestines; Macrophages; Schistosoma; Schistosomiasis

PubMed: 32614982
DOI: 10.1111/imm.13231

Review

Authors: Derek M McKay, Adam Shute, Fernando Lopes...

Approximately one-sixth of the worlds' population is infected with helminths and this class of parasite takes a major toll on domestic livestock. The majority of species of parasitic helminth that infect mammals live in the gut (the only niche for tapeworms) where they contact the hosts' epithelial cells. Here, the helminth-intestinal epithelial interface is reviewed in terms of the impact on, and regulation of epithelial barrier function, both intrinsic (epithelial permeability) and extrinsic (mucin, bacterial peptides, commensal bacteria) elements of the barrier. The data available on direct effects of helminths on epithelial permeability are scant, fragmentary and pales in comparison with knowledge of mobilization of immune reactions and effector cells in response to helminth parasites and how these impact intestinal barrier function. The interaction of helminth-host and helminth-host-bacteria is an important determinant of gut form and function and precisely defining these interactions will radically alter our understanding of normal gut physiology and pathophysiological reactions, revealing new approaches to infection with parasitic helminths, bacterial pathogens and idiopathic auto-inflammatory disease.

Topics: Animals; Helminths; Humans; Intestines

PubMed: 28452686
DOI: 10.1080/21688370.2017.1283385

Authors: Paul McVeigh

Helminth parasitology is an important discipline, which poses often unique technical challenges. One challenge is that helminth parasites, particularly those in humans, are often difficult to obtain alive and in sufficient quantities for study; another is the challenge of studying these organisms in vitro - no helminth parasite life cycle has been fully recapitulated outside of a host. Arguably, the key issue retarding progress in helminth parasitology has been a lack of experimental tools and resources, certainly relative to the riches that have driven many parasitologists to adopt free-living model organisms as surrogate systems. In response to these needs, the past 10-12 years have seen the beginnings of helminth parasitology's journey into the 'omics' era, with the release of abundant sequencing resources, and the functional genomics tools with which to test biological hypotheses. To reflect this progress, the 2019 Autumn Symposium of the British Society for Parasitology was held in Queen's University Belfast on the topic of 'post-genomic progress in helminth parasitology'. This issue presents examples of the current state of play in the field, while this editorial summarizes how genomic datasets and functional genomic tools have stimulated impressive recent progress in our understanding of parasite biology.

Topics: Animals; Anthelmintics; CRISPR-Cas Systems; Drug Resistance; Genome, Helminth; Genomics; Helminthiasis; Helminths; Humans; Parasitology; Pathology, Molecular; Proteomics; RNA Interference; Transcriptome

PubMed: 32252832
DOI: 10.1017/S0031182020000591

Review

Authors: Juan M Inclan-Rico, Mark C Siracusa

Helminth infections represent a significant public health concern resulting in devastating morbidity and economic consequences across the globe. Helminths migrate through mucosal sites causing tissue damage and the induction of type 2 immune responses. Antihelminth protection relies on the mobilization and activation of multiple immune cells, including type 2 innate lymphocytes (ILC2s), basophils, mast cells, macrophages, and hematopoietic stem/progenitor cells. Further, epithelial cells and neurons have been recognized as important regulators of type 2 immunity. Collectively, these pathways stimulate host-protective responses necessary for worm expulsion and the healing of affected tissues. In this review we focus on the innate immune pathways that regulate immunity to helminth parasites and describe how better understanding of these pathways may lead to the development of new therapeutic strategies.

Topics: Animals; Helminthiasis; Helminths; Host-Parasite Interactions; Humans; Immunity, Innate

PubMed: 30177466
DOI: 10.1016/j.pt.2018.08.007

Review

Authors: Blanca E Callejas, Diana Martínez-Saucedo, Luis I Terrazas...

Several environmental factors (chemical, physical, and biological) can cause the initiation, promotion, and progression of cancer. Regarding the biological factors, several studies have found that infections caused by some bacteria, viruses and protozoan, and helminth parasites are related to carcinogenesis. However, in recent years a different approach has been implemented on the antitumor impact of parasitic diseases caused by some protozoan and helminths, mainly because such infections may affect several hallmarks of cancer, but the involved mechanisms still remain unknown. The beneficial effects reported for some parasitic diseases on tumorigenesis range from the induction of apoptosis, activation of the immune response, avoiding metastasis and angiogenesis, inhibition of proliferative signals, to the regulation of inflammatory responses that promote cancer. In this work, we reviewed the available information regarding how parasitic infections may modulate cancer progression. Despite the fact that specific mechanisms of action on tumors are not yet totally clear, we consider that detailed studies of the antitumor action of these organisms and their products could lead to the discovery and use of new molecules from these biological agents that may work as adjuvant therapy in the treatment of various types of cancer.

Topics: Animals; Apoptosis; Carcinogenesis; Disease Progression; Helminths; Host-Parasite Interactions; Humans; Immunity, Active; Neoplasms; Parasitic Diseases

PubMed: 30266743
DOI: 10.1042/BSR20180935

Review

Authors: Anuradha Rajamanickam, Subash Babu

The global prevalence of type 2 diabetes mellitus (T2D) is increasing rapidly, with an anticipated 600 million cases by 2035. While infectious diseases such as helminth infections have decreased due to improved sanitation and health care, recent research suggests a link between helminth infections and T2D, with helminths such as , , , and potentially mitigating or slowing down T2D progression in human and animal models. Helminth infections enhance host immunity by promoting interactions between innate and adaptive immune systems. In T2D, type 1 immune responses are suppressed and type 2 responses are augmented, expanding regulatory T cells and innate immune cells, particularly type 2 immune cells and macrophages. This article reviews recent research shedding light on the favorable effects of helminth infections on T2D. The potential defense mechanisms identified include heightened insulin sensitivity and reduced inflammation. The synthesis of findings from studies investigating parasitic helminths and their derivatives underscores promising avenues for defense against T2D.

Topics: Humans; Animals; Helminthiasis; Diabetes Mellitus, Type 2; Helminths; Insulin Resistance; Risk Factors

PubMed: 38724017
DOI: 10.1146/annurev-nutr-061121-100742

Review

Authors: Henry J McSorley, Mathilde A M Chayé, Hermelijn H Smits...

Type 2 immune responses are most commonly associated with allergy and helminth parasite infections. Since the discovery of Th1 and Th2 immune responses more than 30 years ago, models of both allergic disease and helminth infections have been useful in characterizing the development, effector mechanisms and pathological consequences of type 2 immune responses. The observation that some helminth infections negatively correlate with allergic and inflammatory disease led to a large field of research into parasite immunomodulation. However, it is worth noting that helminth parasites are not always benign infections, and that helminth immunomodulation can have stimulatory as well as suppressive effects on allergic responses. In this review, we will discuss how parasitic infections change host responses, the consequences for bystander immunity and how this interaction influences clinical symptoms of allergy.

Topics: Animals; Helminthiasis; Helminths; Humans; Hypersensitivity; Immunomodulation

PubMed: 30043455
DOI: 10.1111/pim.12574

Review

Authors: Astra S Bryant, Elissa A Hallem

Parasitic helminth infections are the most common source of neglected tropical disease among impoverished global communities. Many helminths infect their hosts via an active, sensory-driven process in which environmentally motile infective larvae position themselves near potential hosts. For these helminths, host seeking and host invasion can be divided into several discrete behaviors that are regulated by both host-emitted and environmental sensory cues, including heat. Thermosensation is a critical sensory modality for helminths that infect warm-blooded hosts, driving multiple behaviors necessary for host seeking and host invasion. Furthermore, thermosensory cues influence the host-seeking behaviors of both helminths that parasitize endothermic hosts and helminths that parasitize insect hosts. Here, we discuss the role of thermosensation in guiding the host-seeking and host-infection behaviors of a diverse group of helminths, including mammalian-parasitic nematodes, entomopathogenic nematodes, and schistosomes. We also discuss the neural circuitry and molecular pathways that underlie thermosensory responses in these species.

Topics: Animals; Behavior; Chemotaxis; Helminths; Humans; Odorants; Temperature; Thermosensing

PubMed: 30336196
DOI: 10.1016/j.neulet.2018.10.023

Authors: Alessio Cantara, Yu Luo, Michaela Dobrovolná...

Parasitic helminths infecting humans are highly prevalent infecting ∼2 billion people worldwide, causing inflammatory responses, malnutrition and anemia that are the primary cause of morbidity. In addition, helminth infections of cattle have a significant economic impact on livestock production, milk yield and fertility. The etiological agents of helminth infections are mainly Nematodes (roundworms) and Platyhelminths (flatworms). G-quadruplexes (G4) are unusual nucleic acid structures formed by G-rich sequences that can be recognized by specific G4 ligands. Here we used the G4Hunter Web Tool to identify and compare potential G4 sequences (PQS) in the nuclear and mitochondrial genomes of various helminths to identify G4 ligand targets. PQS are nonrandomly distributed in these genomes and often located in the proximity of genes. Unexpectedly, a Nematode, Ascaris lumbricoides, was found to be highly enriched in stable PQS. This species can tolerate high-stability G4 structures, which are not counter selected at all, in stark contrast to most other species. We experimentally confirmed G4 formation for sequences found in four different parasitic helminths. Small molecules able to selectively recognize G4 were found to bind to Schistosoma mansoni G4 motifs. Two of these ligands demonstrated potent activity both against larval and adult stages of this parasite.

Topics: Animals; Cattle; G-Quadruplexes; Genome; Helminths; Humans; Ligands; Nematoda; Parasites; Platyhelminths

PubMed: 35234933
DOI: 10.1093/nar/gkac129