Looking beyond the induction of Th2 responses to explain immunomodulation by helminths

Nutman, Thomas B.

doi:10.1111/pim.12194

Cited by 89 publications

(72 citation statements)

References 130 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We conclude that HR hosts, coming from a population with high prevalence of fast growing S. solidus , evolved effective resistance and simultaneous upregulation of proinflammatory innate immune genes and T regulatory components, which diminishes negative effects of the cestode or unspecific side effects such as immunopathology. This result is in line with the good condition of HR hosts and in agreement with the recent emphasis on T regulatory functions in helminth infections (Appendix ; Maizels, ; Maizels & McSorley, ; Maizels & Yazdanbakhsh, ; Nutman, ).…”

Section: Discussionsupporting

confidence: 90%

“…Th1 type cytokines, such as Interleukin‐1β (IL‐1β) and Tumor necrosis factor α (TNF‐α), are proinflammatory; Th2 type cytokines can inhibit Th1 cells and acute‐phase cytokines, induce alternatively activated macrophages, and stimulate B‐cells and antibody production (Liu, Liu, Bleich, Salgame, & Gause, ; Mosmann & Sad, ). Nevertheless, high parasite burdens were described despite increased Th2 responses, which brought another T cell subset into focus, namely immunosuppressive regulatory T (Treg) cells (Maizels, ; Maizels & McSorley, ; Maizels & Yazdanbakhsh, ; Nutman, ). Tregs are considered to be key controllers of immune system homeostasis and expand upon longstanding helminth infections.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The right response at the right time: Exploring helminth immune modulation in sticklebacks by experimental coinfection

2019

View full text Add to dashboard Cite

Parasites are one of the strongest selective agents in nature. They select for hosts that evolve counter‐adaptive strategies to cope with infection. Helminth parasites are special because they can modulate their hosts’ immune responses. This phenomenon is important in epidemiological contexts, where coinfections may be affected. How different types of hosts and helminths interact with each other is insufficiently investigated. We used the three‐spined stickleback (Gasterosteus aculeatus) – Schistocephalus solidus model to study mechanisms and temporal components of helminth immune modulation. Sticklebacks from two contrasting populations with either high resistance (HR) or low resistance (LR) against S. solidus, were individually exposed to S. solidus strains with characteristically high growth (HG) or low growth (LG) in G. aculeatus. We determined the susceptibility to another parasite, the eye fluke Diplostomum pseudospathaceum, and the expression of 23 key immune genes at three time points after S. solidus infection. D. pseudospathaceum infection rates and the gene expression responses depended on host and S. solidus type and changed over time. Whereas the effect of S. solidus type was not significant after three weeks, T regulatory responses and complement components were upregulated at later time points if hosts were infected with HG S. solidus. HR hosts showed a well orchestrated immune response, which was absent in LR hosts. Our results emphasize the role of regulatory T cells and the timing of specific immune responses during helminth infections. This study elucidates the importance to consider different coevolutionary trajectories and ecologies when studying host‐parasite interactions.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The right response at the right time: Exploring helminth immune modulation in sticklebacks by experimental coinfection

2019

View full text Add to dashboard Cite

show abstract

“…In this context, large quantities of IL-5 and IL-13 are primarily produced by ILC-2 cells. IL-5 promotes the eosinophils differentiation and activation which promote IL-4 production, the main primer of CD4 + Th2 cells activation and expansion, with further release of IL-4, IL-5, and IL-13 by this type of cells [3, 60–62]. In this environment, IL-4 and IL-13 induce AAMs, which mainly promote tissue repair and fibrosis by expression of different markers such as arginase-1, Ym1, Ym2, and RELM- α .…”

Section: Discussionmentioning

confidence: 99%

Immune Profile of Honduran Schoolchildren with Intestinal Parasites: The Skewed Response against Geohelminths

Gabrie

Rueda

Rodríguez

et al. 2016

Journal of Parasitology Research

View full text Add to dashboard Cite

Soil-transmitted helminth infections typically induce a type-2 immune response (Th2), but no immunoepidemiological studies have been undertaken in Honduras, an endemic country where the main control strategy is children's annual deworming. We aimed to characterize the immune profile of Honduran schoolchildren harbouring these parasitoses. Demographic and epidemiological data were obtained through a survey; nutritional status was assessed through anthropometry; intestinal parasites were diagnosed by formol-ether and Kato-Katz; and blood samples were collected to determine immunological markers including Th1/Th2 cytokines, IgE, and eosinophil levels. A total of 225 children participated in the study, all of whom had received deworming during the national campaign five months prior to the study. Trichuriasis and ascariasis prevalence were 22.2% and 20.4%, respectively. Stunting was associated with both age and trichuriasis, whereas ascariasis was associated with sex and household conditions. Helminth infections were strongly associated with eosinophilia and hyper-IgE as well as with a Th2-polarized response (increased levels of IL-13, IL-10, and IL4/IFN-γ ratios and decreased levels of IFN-γ). Pathogenic protozoa infections were associated with a Th1 response characterized by elevated levels of IFN-γ and decreased IL10/IFN-γ ratios. Even at low prevalence levels, STH infections affect children's nutrition and play a polarizing role in their immune system.

show abstract

“…Current theories suggest that an expansion in regulatory cell populations (mostly Treg cells, but also macrophages and B cells) and an increase in the secretion of IL-10 and TGF-b, which are observed in both schistosome-infected humans and mice, play a role in dampening the Th2 reaction. However, evidence suggests a more complex, multi-factorial, and systemic effect regulating the longlasting Th2 suppression during chronic schistosomiasis [5,8,9,20,21]. However, evidence suggests a more complex, multi-factorial, and systemic effect regulating the longlasting Th2 suppression during chronic schistosomiasis [5,8,9,20,21].…”

Section: Introductionmentioning

confidence: 99%

Schistosomal extracellular vesicle‐enclosed miRNAs modulate host T helper cell differentiation

et al. 2019

View full text Add to dashboard Cite

During the chronic stage of Schistosoma infection, the female lays fertile eggs, triggering a strong anti-parasitic type 2 helper T-cell (Th2) immune response. It is unclear how this Th2 response gradually declines even though the worms live for years and continue to produce eggs. Here, we show that Schistosoma mansoni downregulates Th2 differentiation in an antigen-presenting cell-independent manner, by modulating the Th2-specific transcriptional program. Adult schistosomes secrete miRNA-harboring extracellular vesicles that are internalized by Th cells in vitro. Schistosomal miRNAs are found also in T helper cells isolated from Peyer's patches and mesenteric lymph nodes of infected mice. In T helper cells, the schistosomal miR-10 targets MAP3K7 and consequently downmodulates NF-jB activity, a critical transcription factor for Th2 differentiation and function. Our results explain, at least partially, how schistosomes tune down the Th2 response, and provide further insight into the reciprocal geographic distribution between high prevalence of parasitic infections and immune disorders such as allergy. Furthermore, this worm-host crosstalk mechanism can be harnessed to develop diagnostic and therapeutic approaches for human schistosomiasis and Th2-associated diseases.

show abstract

Looking beyond the induction of Th2 responses to explain immunomodulation by helminths

Cited by 89 publications

References 130 publications

The right response at the right time: Exploring helminth immune modulation in sticklebacks by experimental coinfection

The right response at the right time: Exploring helminth immune modulation in sticklebacks by experimental coinfection

Immune Profile of Honduran Schoolchildren with Intestinal Parasites: The Skewed Response against Geohelminths

Schistosomal extracellular vesicle‐enclosed miRNAs modulate host T helper cell differentiation

Contact Info

Product

Resources

About