IL‐4/IL‐13‐producing ILC2s are required for timely control of intestinal helminth infection in mice

Varela, Filipa; Symowski, Cornelia; Pollock, Jonathan; Wirtz, Stefan; Voehringer, David

doi:10.1002/eji.202249892

Cited by 7 publications

(4 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, mucosal immunity also plays a role. IL-4 and IL-13 are based on Th2, responsible for stimulating goblet cells to secrete mucin, smooth muscles to contract, and epithelial cells to divide, which all help in expelling helminths from the intestines ( Zhao et al ., 2003 ; Yasuda and Nakanishi, 2018 ; Coakley and Harris, 2020b ; Varela et al ., 2022 ; Atagozli et al ., 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory cell responses in biliary mucosa during Opisthorchis viverrini infection: Insights into susceptibility differences among hosts

Thongrin,

Suyapoh,

Wendo

et al. 2023

Open Vet J

View full text Add to dashboard Cite

Background: Individual host susceptibility is believed to be a risk factor in the interaction between the host and the parasite. Since studying time series in humans is limited, animal models are replaced. Aim: This study aims to explore and compare the pattern of inflammatory cell types along the biliary tract and their association with proliferative lesions in the early development of CCA from susceptible and non-susceptible animal models. Methods: Thirty male Syrian golden hamsters and 30 BALB/c mice, serving as the susceptible and non-susceptible animal models, were used in this comparative study. The animals were infected with 50 O. viverrini metacercariae via gastric intubation. At days 1, 2, 7, 14, 28, and 56 post-infection (p.i.), five animals were randomly selected from each group and humanely sacrificed. The hepatobiliary tissues were collected and processed for histopathological study. Histochemical and immunohistochemical staining were applied to differentiate the inflammatory cell types. Kruskal-Wallis and Mann-Whitney tests were applied to assess all semi-quantitative and quantitative variables. The correlation between each variable was also analyzed using Spearman rank at a p-value <0.05. Results: The results demonstrated that mice had different patterns of infiltrating cell types when compared to hamsters. This suggested that the cellular response to the infection in mice occurred earlier than that in hamsters. The response in mice reached its peak at D7 to D14 and then rapidly declined at D28. In contrast, although the inflammatory response in hamsters started slowly, the response reached the peak at D28 and maintained a high level until D56. Significant differences in the number of inflammatory cells between mice and hamsters were seen at D1 (p=0.047), D7 (p=0.049), D28 (p=0.040), and D56 (p<0.040). Conclusion: The inflammatory responses to O. viverrini infection in the non-susceptible animal model occurred and declined earlier while the response in the susceptible animal model occurred later in a gradual manner. Both rodents are suitable animal models for the studies of opisthorchiasis susceptibility.

show abstract

Section: Discussionmentioning

confidence: 99%

Inflammatory cell responses in biliary mucosa during Opisthorchis viverrini infection: Insights into susceptibility differences among hosts

Thongrin,

Suyapoh,

Wendo

et al. 2023

Open Vet J

View full text Add to dashboard Cite

show abstract

“…In IL-4-treated mice, neutrophils expressed reduced levels of the chemokine receptor CXCR2 relevant for tissue recruitment and more CXCR4 causing retention or recruitment back to the BM [30]. Furthermore, IL-4/IL-13 derived from ILC2s promotes eosinophil recruitment to the lung upon infection of mice with the helminth Nippostrongylus brasiliensis [31]. ILC2s are an important source of IL-5 and regulate eosinophil development and homeostasis [32,33].…”

Section: Tissue Recruitment Of Granulocytes During Inflammationmentioning

confidence: 99%

Granulocyte development, tissue recruitment, and function during allergic inflammation

Radtke

Voehringer

2023

Eur J Immunol

Self Cite

View full text Add to dashboard Cite

Granulocytes provide a fast innate response to pathogens and allergens. In allergy and anti-helminth immunity, epithelial cells of damaged barriers release alarmins like IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) but also chemokines like CXCL1 or CCL11 to promote cell recruitment and inflammation. In addition, mast cells positioned at barrier tissue sites also quickly release mediators upon specifically sensing antigens through IgE bound to FcεR1 on their surface. Released mediators induce the recruitment of different granulocytes in a timely ordered manner. First, neutrophils extravasate from the blood vasculature to the side of alarmin release and promote a potent inflammatory response. Alarmins and activated mast cells further promote activation of ILC2s and recruitment of basophils and eosinophils, which inhibit neutrophil recruitment and enhance tissue type 2 immunity. In addition to their potent pro-inflammatory effector functions, granulocytes can also contribute to termination and resolution of inflammation. Here, we summarize the development and tissue recruitment of granulocyte subsets, and describe general effector functions and aspects of their increasingly appreciated role in limiting tissue damage. We further discuss targeting approaches for therapeutic interventions in allergic disorders.

show abstract

“…In this context, the study of Varela and colleagues provides important insights, since ILC2 4−13ko mice with defective IL-4/IL-13 secretion from ILC2s show impaired worm expulsion, as compared to ILC2 WT mice. However, when IL-4/IL-13 is deleted selectively in T cells, mice exhibit normal NB expulsion, indicating a dispensable role for T cell-derived IL-4/IL-13 in the context of NB infections but emphasizing the role for ILC2-derived IL4/IL-13 in the same setting [134]. Peptides secreted from the enteric nervous system, such as NMU and VIP induce ILC2 effector function, which in turn improve protective immunity towards helminths [63,64,68].…”

Section: Nippostrongylus Brasiliensismentioning

confidence: 99%

ILCs—Crucial Players in Enteric Infectious Diseases

Leupold

Wirtz

2022

IJMS

Self Cite

View full text Add to dashboard Cite

Research of the last decade has remarkably increased our understanding of innate lymphoid cells (ILCs). ILCs, in analogy to T helper (Th) cells and their cytokine and transcription factor profile, are categorized into three distinct populations: ILC1s express the transcription factor T-bet and secrete IFNγ, ILC2s depend on the expression of GATA-3 and release IL-5 and IL-13, and ILC3s express RORγt and secrete IL-17 and IL-22. Noteworthy, ILCs maintain a level of plasticity, depending on exposed cytokines and environmental stimuli. Furthermore, ILCs are tissue resident cells primarily localized at common entry points for pathogens such as the gut-associated lymphoid tissue (GALT). They have the unique capacity to initiate rapid responses against pathogens, provoked by changes of the cytokine profile of the respective tissue. Moreover, they regulate tissue inflammation and homeostasis. In case of intracellular pathogens entering the mucosal tissue, ILC1s respond by secreting cytokines (e.g., IFNγ) to limit the pathogen spread. Upon infection with helminths, intestinal epithelial cells produce alarmins (e.g., IL-25) and activate ILC2s to secrete IL-13, which induces differentiation of intestinal stem cells into tuft and goblet cells, important for parasite expulsion. Additionally, during bacterial infection ILC3-derived IL-22 is required for bacterial clearance by regulating antimicrobial gene expression in epithelial cells. Thus, ILCs can limit infectious diseases via secretion of inflammatory mediators and interaction with other cell types. In this review, we will address the role of ILCs during enteric infectious diseases.

show abstract

IL‐4/IL‐13‐producing ILC2s are required for timely control of intestinal helminth infection in mice

Cited by 7 publications

References 34 publications

Inflammatory cell responses in biliary mucosa during Opisthorchis viverrini infection: Insights into susceptibility differences among hosts

Inflammatory cell responses in biliary mucosa during Opisthorchis viverrini infection: Insights into susceptibility differences among hosts

Granulocyte development, tissue recruitment, and function during allergic inflammation

ILCs—Crucial Players in Enteric Infectious Diseases

Contact Info

Product

Resources

About