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Helminths, immune

Marcelo Arantes Levenhagen, Hélio Conte, Julia Maria Costa-Cruz
Strongyloides stercoralis is a helminth parasite that can infect millions of people worldwide, particularly in tropical, subtropical and temperate regions with poor sanitation. Several aspects of epidemiology, biology and host-parasite interactions of S. stercoralis have been studied, and substantial knowledge has been acquired; however, very few studies on immunotherapeutic control strategies to prevent infection and disease in humans have been conducted. Therefore, this article reviews the current progress and targets toward vaccine and passive immunization approaches for Strongyloides spp...
October 18, 2016: Immunology Letters
Alexandre P Meli, Ghislaine Fontés, Danielle T Avery, Scott A Leddon, Mifong Tam, Michael Elliot, Andre Ballesteros-Tato, Jim Miller, Mary M Stevenson, Deborah J Fowell, Stuart G Tangye, Irah L King
T follicular helper (Tfh) cells are a CD4(+) T cell subset critical for long-lived humoral immunity. We hypothesized that integrins play a decisive role in Tfh cell biology. Here we show that Tfh cells expressed a highly active form of leukocyte function-associated antigen-1 (LFA-1) that was required for their survival within the germinal center niche. In addition, LFA-1 promoted expression of Bcl-6, a transcriptional repressor critical for Tfh cell differentiation, and inhibition of LFA-1 abolished Tfh cell generation and prevented protective humoral immunity to intestinal helminth infection...
October 18, 2016: Immunity
Anders Dige, Tue Kruse Rasmussen, Peter Nejsum, Rikke Hagemann-Madsen, Andrew R Williams, Jørgen Agnholt, Jens F Dahlerup, Christian L Hvas
Helminthic therapy of immune-mediated diseases has gained attention in recent years, but we know little of how helminths modulate human immunity. In this study, we investigated how self-infection with Trichuris (T.) trichiura in an adult man without intestinal disease affected mucosal and systemic immunity. Colonic mucosal biopsies were obtained at baseline, during T. trichiura infection, and after its clearance following mebendazole treatment. Unexpectedly, the volunteer experienced a Campylobacter colitis following T...
October 15, 2016: Parasite Immunology
Kazunobu Asano, Zhiliang Wu, Piyarat Srinontong, Takahide Ikeda, Isao Nagano, Hirokuyi Morita, Yoichi Maekawa
Infectious microorganisms often modify host immunity to escape from immune elimination. Trichinella is a unique nematode of the helminth family, which parasitize the inside of host muscle cells without robust eliminative reactions. There are two main species in genus Trichinella, encapsulated (T. spiralis(Ts), T. britovi) and non-encapsulated (T. pseudospiralis(Tp)). It has already been established that Trichinella infection affects host immune responses in several experimental immune diseases in animal models; however, most of those studies were done using Ts infection...
October 10, 2016: Infection and Immunity
Haggai Bar-Yoseph, Yaniv Zohar, Margalit Lorber
Helminthic infection and HIV have been reported to coexist, particularly in sub-Saharan African patients living with HIV. Strongyloidiasis is one of the most common helminths, usually leading to cutaneous and gastrointestinal (GI) symptoms. In the immunocompromised host, this infection can lead to strongyloidiasis hyperinfection syndrome (SHS), not common in HIV-infected patients. Immune reconstitution inflammatory syndrome (IRIS) can follow the initiation of antiretroviral therapy (ART), with a variety of presentations...
October 12, 2016: Journal of the International Association of Providers of AIDS Care
Eduardo de la Torre-Escudero, Adam P S Bennett, Alexzandra Clarke, Gerard P Brennan, Mark W Robinson
The recent discovery that parasites release extracellular vesicles (EVs) that can transfer a range of effector molecules to host cells has made us re-think our understanding of the host-parasite interface. In this opinion article we consider how recent proteomics and transcriptomics studies, together with ultrastructural observations, suggest that more than one mechanism of EV biogenesis can occur in helminths. We propose that distinct EV subtypes have roles in immune modulation and repair of drug-induced damage, and put forward the case for targeting EV biogenesis pathways to achieve parasite control...
October 5, 2016: Trends in Parasitology
Raquel Alvarado, Joyce To, Maria E Lund, Anita Pinar, Ashley Mansell, Mark W Robinson, Bronwyn A O'Brien, John P Dalton, Sheila Donnelly
The NLRP3 inflammasome is a multimeric protein complex that controls the production of IL-1β, a cytokine that influences the development of both innate and adaptive immune responses. Helminth parasites secrete molecules that interact with innate immune cells, modulating their activity to ultimately determine the phenotype of differentiated T cells, thus creating an immune environment that is conducive to sustaining chronic infection. We show that one of these molecules, FhHDM-1, a cathelicidin-like peptide secreted by the helminth parasite, Fasciola hepatica, inhibits the activation of the NLRP3 inflammasome resulting in reduced secretion of IL-1β by macrophages...
September 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ralf Willebrand, David Voehringer
PURPOSE OF REVIEW: Eosinophils are a subset of granulocytes generally associated with type 2 immune responses. They can contribute to protection against helminths but also mediate pro-inflammatory functions during allergic immune responses. Only recently, eosinophils were also found to exert many other functions such as regulation of glucose and fat metabolism, thermogenesis, survival of plasma cells, and antitumor activity. The mechanisms that control eosinophil development and survival are only partially understood...
September 26, 2016: Current Opinion in Hematology
José L Reyes, Fernando Lopes, Gabriella Leung, Nicole L Mancini, Chelsea E Matisz, Arthur Wang, Emma A Thomson, Nicholas Graves, John Gilleard, Derek M McKay
Awareness of the immunological underpinnings of host-parasite interactions may reveal immune signaling pathways that could be used to treat inflammatory disease in humans. Previously we showed that infection with the rat tapeworm Hymenolepis diminuta, used as a model helminth, or systemic delivery of worm antigen (HdAg) significantly reduced the severity of dinitrobenzene sulphonic acid (DNBS)-induced colitis in mice. Extending these analyses, intraperitoneal injection of HdAg dose-dependently suppressed dextran sodium sulphate (DSS)-induced colitis and this was paralleled by reduced IFNγ, IL-17 and TNFα and increased IL-10 production from mitogen-activated splenocytes...
September 26, 2016: Infection and Immunity
N P Amdare, V K Khatri, R S P Yadav, A Tarnekar, K Goswami, M V R Reddy
Epidemiological and experimental evidence has supported the concept of using helminths as alternative bio-therapeutic agents in the treatment of type 1 diabetes (T1D). In the current study, two filarial proteins, recombinant Wuchereria bancrofti L2 (rWbL2) and Brugia malayi abundant larval transcript 2 (rBmALT-2) have been investigated, individually and in combination, for their therapeutic potential in streptozotocin (STZ)-induced T1D. The rWbL2 and rBmALT-2 proteins, when administered individually or in combination, have resulted in lowering of the blood glucose levels and reducing the incidence of T1D in mice...
September 26, 2016: Journal of Helminthology
Michael D Gurven, Benjamin C Trumble, Jonathan Stieglitz, Aaron D Blackwell, David E Michalik, Caleb E Finch, Hillard S Kaplan
Heart disease and type 2 diabetes are commonly believed to be rare among contemporary subsistence-level human populations, and by extension prehistoric populations. Although some caveats remain, evidence shows these diseases to be unusual among well-studied hunter-gatherers and other subsistence populations with minimal access to healthcare. Here we expand on a relatively new proposal for why these and other populations may not show major signs of these diseases. Chronic infections, especially helminths, may offer protection against heart disease and diabetes through direct and indirect pathways...
September 25, 2016: Evolution, Medicine, and Public Health
Motoko Morimoto, Noritsugu Azuma, Hikaru Kadowaki, Tatsuya Abe, Yoshiko Suto
Helminth-induced type 2 cytokines increase the number of regulatory T cells and alternatively activated macrophages, resulting in modulation of the host-immune system. Studies on these parasite-induced immunoregulatory mechanisms might contribute to the development of new therapies for inflammatory diseases, including type 2 diabetes (T2D). Previous studies have suggested that progression of obesity-associated metabolic abnormalities is under pathophysiological control of CD4+ T cells. Glucose absorption through the intestinal epithelium reduced after infection in a STAT-6-dependent manner...
September 22, 2016: Journal of Veterinary Medical Science
Carla Muñoz-Antoli, Alba Cortés, Rebeca Santano, Javier Sotillo, J Guillermo Esteban, Rafael Toledo
Echinostoma caproni is an intestinal trematode that has been extensively used as an experimental model to investigate the factors determining the resistance to intestinal helminths or the development of chronic infections. ICR mice are permissive hosts for E. caproni in which chronic infections are developed, concomitantly with local Th1 responses, elevated levels of local IFN-γ, inflammation and antibody responses. However, mice develop partial resistance to homologous challenge infections after cure of a primary infection, which converts this subject into an adequate model for the study of the mechanisms generating resistance against intestinal helminths...
2016: Scientific Reports
Berenice Faz-López, Jorge Morales-Montor, Luis I Terrazas
The Th1/Th2/Th17 balance is a fundamental feature in the regulation of the inflammatory microenvironment during helminth infections, and an imbalance in this paradigm greatly contributes to inflammatory disorders. In some cases of helminthiasis, an initial Th1 response could occur during the early phases of infection (acute), followed by a Th2 response that prevails in chronic infections. During the late phase of infection, alternatively activated macrophages (AAMs) are important to counteract the inflammation caused by the Th1/Th17 response and larval migration, limiting damage and repairing the tissue affected...
2016: BioMed Research International
Sina Brückner, Selidji Todagbe Agnandji, Johannes Elias, Stefan Berberich, Emmanuel Bache, José Fernandes, Marguerite Massinga Loembe, Johanna Hass, Bertrand Lell, Benjamin Mordmüller, Ayola Akim Adegnika, Peter Kremsner, Meral Esen
BACKGROUND: We recently described the effect of a single-dose antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine. Here we report the effect of antihelminthics on the immunogenicity of a meningococcal vaccine and a cholera vaccine in primary school children living in Lambaréné, Gabon. Since infection with helminths remains a major public health problem and the influence on cognitive and physical development as well as the immunomodulatory effects are well established, we investigated if a single-dose antihelminthic treatment prior to immunization positively influences antibody titers and vaccine-specific memory B-cells...
October 17, 2016: Vaccine
Luis Janssen, Gisele Lorranna Silva Santos, Herick Sampaio Muller, Anderson Rodrigues Araújo Vieira, Tatiana Amabile de Campos, Vicente de Paulo Martins
It is long known that some parasite infections are able to modulate specific pathways of host's metabolism and immune responses. This modulation is not only important in order to understand the host-pathogen interactions and to develop treatments against the parasites themselves but also important in the development of treatments against autoimmune and inflammatory diseases. Throughout the life cycle of schistosomes the mammalian hosts are exposed to several biomolecules that are excreted/secreted from the parasite infective stage, named cercariae, from their tegument, present in adult and larval stages, and finally from their eggs...
2016: Journal of Immunology Research
Neima Briggs, Jill Weatherhead, K Jagannadha Sastry, Peter J Hotez
Current iterations of the hygiene hypothesis suggest an adaptive role for helminth parasites in shaping the proper maturation of the immune system. However, aspects of this hypothesis are based on assumptions that may not fully account for realities about human helminth infections. Such realities include evidence of causal associations between helminth infections and asthma or inflammatory bowel disease as well as the fact that helminth infections remain widespread in the United States, especially among populations at greatest risk for inflammatory and autoimmune diseases...
September 2016: PLoS Neglected Tropical Diseases
Yogesh Singh, Yuetao Zhou, Xiaolong Shi, Shaqiu Zhang, Anja T Umbach, Madhuri S Salker, Karl S Lang, Florian Lang
CD4+ T helper 9 (Th9) cells are a newly discovered Th cell subset that produce the pleiotropic cytokine IL-9. Th9 cells can protect against tumours and provide resistance against helminth infections. Given their pivotal role in the adaptive immune system, understanding Th9 cell development and the regulation of IL-9 production could open novel immunotherapeutic opportunities. The Na+/H+ exchanger 1 (NHE1) is critically important for regulating intracellular pH (pHi), cell volume, migration and cell survival...
September 14, 2016: Journal of Biological Chemistry
Menno J Oudhoff, Frann Antignano, Alistair L Chenery, Kyle Burrows, Stephen A Redpath, Mitchell J Braam, Georgia Perona-Wright, Colby Zaph
The intestine is a common site for a variety of pathogenic infections. Helminth infections continue to be major causes of disease worldwide, and are a significant burden on health care systems. Lysine methyltransferases are part of a family of novel attractive targets for drug discovery. SETD7 is a member of the Suppressor of variegation 3-9-Enhancer of zeste-Trithorax (SET) domain-containing family of lysine methyltransferases, and has been shown to methylate and alter the function of a wide variety of proteins in vitro...
September 2016: PLoS Pathogens
Alistair L Chenery, Frann Antignano, Michael R Hughes, Kyle Burrows, Kelly M McNagny, Colby Zaph
Pro-inflammatory cytokines produced during immune responses to infectious stimuli are well-characterized to have secondary effects on the function of hematopoietic progenitor cells in the bone marrow (BM). However, these effects on the BM are poorly characterized during chronic infection with intestinal helminth parasites. In this study, we use the Trichuris muris model of infection and show that Th1 cell-associated, but not acute Th2 cell-associated, responses to chronic T. muris infection cause a major, transient expansion of CD48(-) CD150(-) multipotent progenitor cells in the BM that is dependent on the presence of adaptive immune cells and IFN-γ signalling...
September 4, 2016: European Journal of Immunology
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