The Study of Host Immune Responses Elicited by the Model Murine Hookworms <i>Nippostrongylus brasiliensis</i> and <i>Heligmosomoides polygyrus</i>

Bouchery, Tiffany; Volpe, Beatrice; Shah, Kathleen; Lebon, Luc; Filbey, Kara J.; Gros, Graham Le; Harris, Nicola L.

doi:10.1002/cpmo.34

Cited by 31 publications

(56 citation statements)

References 75 publications

(131 reference statements)

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“…A). To induce type 2 inflammation in the lung, mice were infected s.c. with Nb larvae, which migrate through the lung within the first few days of infection and translocate to the intestine by day 3, where they develop into mature adults and produce eggs, which are expelled in the feces . When mice were analyzed on days 5, 7, and 9 after infection, we observed that the frequency and total cell number of ILC2s steadily increased in the lung of infected WT mice and this response was significantly reduced in 4–13Tko and 4–13ko mice (Fig.…”

Section: Resultsmentioning

confidence: 81%

“…IL‐4/IL‐13‐deficient mice (4‐13ko) were kindly provided by A.N. McKenzie (MRC Laboratory of Molecular Biology, Cambridge, UK) . Mice with a loxP‐flanked IL‐4/IL‐13 allele were crossed to CD4Cre mice to generate mice with selective deletion of both cytokines in T cells (4‐13Tko mice) and backcrossed for more than ten generations to BALB/c background.…”

Section: Methodsmentioning

confidence: 99%

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Th2 cell‐derived IL‐4/IL‐13 promote ILC2 accumulation in the lung by ILC2‐intrinsic STAT6 signaling in mice

Symowski

Voehringer

2019

Eur J Immunol

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Type 2 innate lymphoid cells (ILC2s) are largely tissue-resident cytokine-secreting effector cells associated with allergic inflammation and protective immunity against helminths. Mechanisms that regulate the population dynamics of ILC2s in tissues are poorly understood. In this issue, Symowski C. and Voehringer D. show that Th2 cell-derived IL-4/IL-13 enhance the proliferation and accumulation of ILC2s in the lung of mice infected with the helminth Nippostrongylus brasiliensis. By generating mixed bone marrow chimeras, the authors could demonstrate that this effect requires ILC2-intrinsic expression of STAT6. STAT6-deficient ILC2s showed lower expression of MHC class II molecules on the cell surface suggesting that ILC2s may communicate directly with Th2 cells and receive an antigen-dependent positive feedback signal that leads to ILC2 accumulation in the lung.

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Section: Resultsmentioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Th2 cell‐derived IL‐4/IL‐13 promote ILC2 accumulation in the lung by ILC2‐intrinsic STAT6 signaling in mice

Symowski

Voehringer

2019

Eur J Immunol

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“…The transmembrane glycoprotein F4/80 (112) was later identified as a tissue-resident macrophage-specific marker in various tissues, including the gastrointestinal tract (113), bone marrow (114), and lymphoid organs (115). Its expression on murine gastrointestinal macrophages (116,117) makes it a widely used panmacrophage marker in models of intestinal helminth infection (113,118,119). However, when F4/80 was found to be expressed on murine eosinophils in 1991 (24), the use of F4/80 as a macrophage-specific marker became controversial (120,121).…”

Section: Reinterpreting Results and Use Of New Technologiesmentioning

confidence: 99%

“…In mice, macrophages in helminth-induced Th2 granulomas are identified using the surface marker F4/80 (113,118,119). F4/80 plays a role in inducing efferent CD8 ϩ regulatory T cells, mediating peripheral tolerance (183,184).…”

Section: Mouse-to-human Translatabilitymentioning

confidence: 99%

Eosinophils and Macrophages within the Th2-Induced Granuloma: Balancing Killing and Healing in a Tight Space

Ariyaratne

Finney

2019

Infect Immun

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Granuloma formation is a key host immune response generated to confine invading pathogens and limit extensive host damage. It consists of an accumulation of host immune cells around a pathogen. This host response has been extensively studied in the context of inflammatory diseases. However, there is much less known about Th2-type granulomas generated in response to parasitic worms. Based onin vitrodata, innate immune cells within the granuloma are thought to immobilize and kill parasites but also act to repair damaged tissue. Understanding this dual function is key. The two billion people and many livestock/wild animals infected with helminths demonstrate that granulomas are not effective at clearing infection. However, the lack of high mortality highlights their importance in ensuring that parasite migration/tissue damage is restricted and wound healing is effective. In this review, we define two key cellular players (macrophages and eosinophils) and their associated molecular players involved in Th2 granuloma function. To date, the underlying mechanisms remain poorly understood, which is in part due to a lack of conclusive studies. Most have been performedin vitrorather thanin vivo, using cells that have not been obtained from granulomas. Experiments using genetically modified mouse strains and/or antibody/chemical-mediated cell depletion have also generated conflicting results depending on the model. We discuss the caveats of previous studies and the new tools available that will help fill the gaps in our knowledge and allow a better understanding of the balance between immune killing and healing.

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“…Many parasitic helminths, including Hpb exhibit a sexual reproductive cycle resulting in large genetic heterogeneity amongst individual worms. Even parasites maintained in laboratories for use in experimental work are produced in batches that can each be considered as different communities and may show significant differences including in term of virulence (11, 21). To test the impact of distinct parasite batches on helminth-induced microbial changes, we assessed the impact of two distinct batches of worms on the same microbiome by performing a large experiment in which all mice were subjected to ‘normalization’ of the ‘starting intestinal microbiome’ by mixing beddings between cages and randomizing mice once a week for four weeks prior to infection (Fig 1).…”

Section: Resultsmentioning

confidence: 99%

Infection with a small intestinal helminth Heligmosomoides polygyrus bakeri consistently alters microbial communities throughout the small and large intestine

Harris

Rapin²,

Chuat

et al. 2019

Preprint

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Increasing evidence suggests that intestinal helminth infection can alter intestinal microbial communities with important impacts on the mammalian host. However, all of the studies to date utilize different techniques to study the microbiome and access different sites of the intestine with little consistency noted between studies. In the present study, we set out to perform a comprehensive analysis of the impact of intestinal helminth infection on the mammalian intestinal bacterial microbiome. For this purpose, we investigated the impact of experimental infection using the natural murine small intestinal helminth, Heligmosomoides polygyrus bakeri (Hpb) and examined possible alterations in both the mucous and luminal bacterial communities along the entire small and large intestine. We also explored the impact of common experimental variables, including the parasite batch and pre-infection microbiome, on the outcome of helminth-bacterial interactions. This work provides evidence that helminth infection reproducibly alters intestinal microbial communities – with an impact of infection noted along the entire length of the intestine. Although the exact nature of helminth-induced alterations to the intestinal microbiome differed depending on the parasite batch and microbiome community structure present prior to infection, changes extended well beyond the introduction of new bacterial species by the infecting larvae. Moreover, striking similarities between different experiments were noted, including the consistent outgrowth of a bacterium belonging to the Peptostreptococcaceae family throughout the intestine. Author Summary Increasing evidence indicates a role for interactions between intestinal helminths and the microbiome in regulating mammalian health, and a greater understanding of helminth-microbiota interactions may open the path for the development of novel immunomodulatory therapies. However, such studies are hampered by the inconsistent nature of the data reported so far. Such inconsistancies likely result from variations in the experimental and technological methodologies employed to investigate helminth-microbiota interactions and well has natural variation in the starting microbiome composition and/or worm genetics. We conducted a thorough study in which the reproducibility of helminth-induced alterations of microbial communities was determined and impact of common experimental variables – such as the starting microbiome and parasite batch - was determined. Our work reveals the robust ability of small intestinal helminth infection to alter microbial communities along the entire length of the intestine and additionally identifies a single bacterium that is strongly associated with infection across multiple experiments.

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The Study of Host Immune Responses Elicited by the Model Murine Hookworms Nippostrongylus brasiliensis and Heligmosomoides polygyrus

Cited by 31 publications

References 75 publications

Th2 cell‐derived IL‐4/IL‐13 promote ILC2 accumulation in the lung by ILC2‐intrinsic STAT6 signaling in mice

Th2 cell‐derived IL‐4/IL‐13 promote ILC2 accumulation in the lung by ILC2‐intrinsic STAT6 signaling in mice

Eosinophils and Macrophages within the Th2-Induced Granuloma: Balancing Killing and Healing in a Tight Space

Infection with a small intestinal helminth Heligmosomoides polygyrus bakeri consistently alters microbial communities throughout the small and large intestine

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