IL-33 facilitates rapid expulsion of the parasitic nematode Strongyloides ratti from the intestine via ILC2- and IL-9-driven mast cell activation

Meiners, Jana; Reitz, Martina; Rüdiger, Nikolas; Turner, Jan-Eric; Heepmann, Lennart; Rudolf, Lena; Hartmann, Wiebke; McSorley, Henry J.; Breloer, Minka

doi:10.1371/journal.ppat.1009121

Cited by 31 publications

(28 citation statements)

References 50 publications

(129 reference statements)

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“…When mast cells are exposed to bacterial toxins, they recruit neutrophilic granulocytes and release pro-inflammatory mediators such as IL −6, TNF-α, and lipid mediators, thereby eliminating the bacteria and reducing bacterial colonization [ 5 , 8 ]. Moreover, the importance of mast cells in parasitic infections has also been demonstrated in Strongyloides ratti , where the mast cell deficient model showed impaired parasite defense and slowed response to the alarmin IL −33 [ 9 ]. Although mast cell activation is essential for the body’s defense against infection, inappropriate activation can lead to deleterious results.…”

Section: The Role Of Mast Cells In Diseasementioning

confidence: 99%

The role of human mast cells in allergy and asthma

et al. 2022

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Mast cells are tissue-inhabiting cells that play an important role in inflammatory diseases of the airway tract. Mast cells arise in the bone marrow as progenitor cells and complete their differentiation in tissues exposed to the external environment, such as the skin and respiratory tract, and are among the first to respond to bacterial and parasitic infections. Mast cells express a variety of receptors that enable them to respond to a wide range of stimulants, including the high-affinity FcεRI receptor. Upon initial contact with an antigen, mast cells are sensitized with IgE to recognize the allergen upon further contact. FcεRI-activated mast cells are known to release histamine and proteases that contribute to asthma symptoms. They release a variety of cytokines and lipid mediators that contribute to immune cell accumulation and tissue remodeling in asthma. Mast cell mediators trigger inflammation and also have a protective effect. This review aims to update the existing knowledge on the mediators released by human FcεRI-activated mast cells, and to unravel their pathological and protective roles in asthma and allergy. In addition, we highlight other diseases that arise from mast cell dysfunction, the therapeutic approaches used to address them, and fill the gaps in our current knowledge. Mast cell mediators not only trigger inflammation but may also have a protective effect. Given the differences between human and animal mast cells, this review focuses on the mediators released by human FcεRI-activated mast cells and the role they play in asthma and allergy.

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Section: The Role Of Mast Cells In Diseasementioning

confidence: 99%

The role of human mast cells in allergy and asthma

et al. 2022

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“…Given that ILC2s were previously shown to mediate protective immune responses against different intestinal helminths i.e. in S. ratti infection through mast cell activation and N. brasiliensis infection through involvement in maintenance of alternatively activated macrophages ( 15 , 35 ), we speculated that ILC2s are also involved in protective immune responses against L. sigmodontis infection in semi-susceptible C57BL/6 mice. To investigate the role of ILC2s during L. sigmodontis infection by depletion experiments, we used T and B cell-deficient Rag2 -/- C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 99%

ILC2s Control Microfilaremia During Litomosoides sigmodontis Infection in Rag2-/- Mice

et al. 2022

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Group 2 innate lymphoid cells (ILC2s) are inducers of type 2 immune responses, but their role during filarial infection remains unclear. In the present study, we used the Litomosoides sigmodontis rodent model of filariasis to analyze ILC2s during infection in susceptible BALB/c mice that develop a chronic infection with microfilaremia and semi-susceptible C57BL/6 mice that eliminate the filariae shortly after the molt into adult worms and thus do not develop microfilaremia. ILC2s (CD45+ Lineage- TCRβ- CD90.2+ Sca-1+ IL-33R+ GATA-3+) were analyzed in the pleural cavity, the site of L. sigmodontis infection, after the infective L3 larvae reached the pleural cavity (9 days post infection, dpi), after the molt into adult worms (30dpi) and during the peak of microfilaremia (70dpi). C57BL/6 mice had significantly increased ILC2 numbers compared to BALB/c mice at 30dpi, accompanied by substantially higher IL-5 and IL-13 levels, indicating a stronger type 2 immune response in C57BL/6 mice upon L. sigmodontis infection. At this time point the ILC2 numbers positively correlated with the worm burden in both mouse strains. ILC2s and GATA-3+ CD4+ T cells were the dominant source of IL-5 in L. sigmodontis-infected C57BL/6 mice with ILC2s showing a significantly higher IL-5 expression than CD4+ T cells. To investigate the importance of ILC2s during L. sigmodontis infection, ILC2s were depleted with anti-CD90.2 antibodies in T and B cell-deficient Rag2-/- C57BL/6 mice on 26-28dpi and the outcome of infection was compared to isotype controls. Rag2-/- mice were per se susceptible to L. sigmodontis infection with significantly higher worm burden than C57BL/6 mice and developed microfilaremia. Depletion of ILC2s did not result in an increased worm burden in Rag2-/- mice, but led to significantly higher microfilariae numbers compared to isotype controls. In conclusion, our data demonstrate that ILC2s are essentially involved in the control of microfilaremia in Rag2-/- C57BL/6 mice.

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“…Mast cells are a main target of IL-9, which serves as a growth factor for these cells and also in uences their function 36,37 . The present study demonstrated that mast cell accumulation in the lung tissue of HDM-challenged mice was clearly attenuated by IL-9 de ciency, and this was supported by the reduction of mMCP-1 in the lung tissue homogenate of the experimental animals.…”

Section: Discussionmentioning

confidence: 99%

The Absence of IL-9 Reduces Allergic Airway Inflammation by Reducing ILC2, Th2 and Mast Cells in Murine Model of Asthma

Feng

Yang

et al. 2022

Preprint

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Asthma is an allergic inflammatory disease of the airways, in which numerous cell types and cytokines have been shown to contribute to pathogenesis of the disease. Although increased expression of IL-9 has been shown to influence the activity of structural as well as eosinophils and mast cells in asthma, the influence of IL-9 on function of ILC2 and Th2 cells remains unclear. This study therefore aimed to elucidate the role of IL-9 on ILC2 and Th2 cells using a murine model of asthma. A murine model of asthma was established using wild type (WT) and IL-9-deficient (Il9−/−) transgenic mice sensitized to house dust mite (HDM). Bronchoalveolar lavage fluid (BALF) and lung tissues were collected, and analysed for inflammatory cells (eosinophils, mast cells, Th2 cells and ILC2 cells), histopathological changes, and several cytokines. HDM challenge significantly increased accumulation of ILC2 cells, Th2 cells and mast cells, as well as goblet cell hyperplasia, and the expression of cytokines IL-4, IL-5 and IL-13, but not IFN-γ, in WT mice compared to saline-challenged control group. In contrast, all pathological changes, including infiltration of ILC2 cells, Th2 cells and mast cells, were significantly attenuated in HDM-challenged Il9−/− mice. Furthermore, the number of Ki67+ILC2 cells, Ki67+Th2 cells and Ki67+mast cells were significantly reduced in the absence of IL-9 signalling. These data suggest that IL-9 promotes the proliferation and type 2 cytokine production of type 2 cells in the murine models of asthma, and therefore might be a potential therapeutic target for asthma treatment.

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IL-33 facilitates rapid expulsion of the parasitic nematode Strongyloides ratti from the intestine via ILC2- and IL-9-driven mast cell activation

Cited by 31 publications

References 50 publications

The role of human mast cells in allergy and asthma

The role of human mast cells in allergy and asthma

ILC2s Control Microfilaremia During Litomosoides sigmodontis Infection in Rag2-/- Mice

The Absence of IL-9 Reduces Allergic Airway Inflammation by Reducing ILC2, Th2 and Mast Cells in Murine Model of Asthma

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