Modes of type 2 immune response initiation

Kopp, Elizabeth; Agaronyan, Karen; Licona‐Limón, Ileana; Nish, Simone A.; Medzhitov, Ruslan

doi:10.1016/j.immuni.2023.03.015

Cited by 14 publications

(5 citation statements)

References 70 publications

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“…ability to induce allergic sensitisation or conditions prone to it); and (vi) non‐IgE‐mediated allergy to proteins such as eosinophilic esophagitis or other gastrointestinal disorders (Akdis, 2021 ; Caminero et al., 2023 ; EFSA GMO Panel, 2017 ; Hang et al., 2019 ; Le Gall et al., 2011 ; Lee et al., 2022 ; Levan et al., 2019 ; Lloyd‐Price et al., 2019 ; Platts‐Mills et al., 2021 ; Plum et al., 2023 ; Sharma & Karim, 2021 ; Sozener et al., 2022 ). In allergic disease, adjuvants alter tissue homeostasis to establish conditions that result in non‐specific, innate type 2 (allergic) priming to bystander allergens, thus subverting the development of tolerance (Akdis, 2021 ; Bruton et al., 2020 ; Ellenbogen et al., 2018 ; Kopp et al., 2023 ). In relation to non‐IgE‐mediated adverse immune reactions to food, detailed risk assessment considerations are provided for the safety profile of the protein or peptide and its potential to cause coeliac disease (EFSA GMO Panel, 2017 ).…”

Section: Assessmentmentioning

confidence: 99%

New developments in biotechnology applied to microorganisms

Mullins,

Bresson,

Dewhurst

et al. 2024

EFS2

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EFSA was requested by the European Commission (in accordance with Article 29 of Regulation (EC) No 178/2002) to provide a scientific opinion on the application of new developments in biotechnology (new genomic techniques, NGTs) to viable microorganisms and products of category 4 to be released into the environment or placed on the market as or in food and feed, and to non‐viable products of category 3 to be placed on the market as or in food and feed. A horizon scanning exercise identified a variety of products containing microorganisms obtained with NGTs (NGT‐Ms), falling within the remit of EFSA, that are expected to be placed on the (EU) market in the next 10 years. No novel potential hazards/risks from NGT‐Ms were identified as compared to those obtained by established genomic techniques (EGTs), or by conventional mutagenesis. Due to the higher efficiency, specificity and predictability of NGTs, the hazards related to the changes in the genome are likely to be less frequent in NGT‐Ms than those modified by EGTs and conventional mutagenesis. It is concluded that EFSA guidances are ‘partially applicable’, therefore on a case‐by‐case basis for specific NGT‐Ms, fewer requirements may be needed. Some of the EFSA guidances are ‘not sufficient’ and updates are recommended. Because possible hazards relate to genotypic and phenotypic changes introduced and not to the method used for the modification, it is recommended that any new guidance should take a consistent risk assessment approach for strains/products derived from or produced with microorganisms obtained with conventional mutagenesis, EGTs or NGTs.

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Section: Assessmentmentioning

confidence: 99%

New developments in biotechnology applied to microorganisms

Mullins,

Bresson,

Dewhurst

et al. 2024

EFS2

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“…While T H 2 cells are described as being producers of IL-4, IL-5, and IL-13, studies using cytokine reporter mice found that T cells, in this case CXCR5+PD1+ T follicular helper cells (T FH ), only produce IL-4 in lymph nodes in response to parasite infection, whereas they dominantly produce IL-5 and IL-13 after entering peripheral tissues such as the lungs [ 5 ]. This suggests that full T H 2 differentiation is a multistep process that requires initial priming in the lymph node followed by confirmation signals encountered in tissues, such as IL-33 [ 6 , 7 ]. On the other hand, in response to fungal challenges such as Alternaria alternata extract, T FH cells can produce IL-13 that helps promote IgE class switch recombination in B cells [ 8 ].…”

Section: Cellular Response Pathways In Type 2 Immunitymentioning

confidence: 99%

“…Upon ligand binding, CLRs direct the differentiation of T H 17 responses to promote anti-fungal immune responses [ 65 ]. As has been alluded to in this review, T H 2 responses seem to obey different rules as there are no known DC-expressed PRRs that exclusively drive T H 2 differentiation in response to antigen [ 6 ]. In the context of house dust mite (HDM) allergy, Dectin-1 and Dectin-2 have been reported to participate in T H 2 differentiation [ 66 – 69 ].…”

Section: Cellular Response Pathways In Type 2 Immunitymentioning

confidence: 99%

Novel mechanistic insights underlying fungal allergic inflammation

Zheng,

Dang

2023

PLoS Pathog

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The worldwide prevalence of asthma and allergic disorders (allergic rhinitis, atopic dermatitis, food allergy) has been steadily rising in recent decades. It is now estimated that up to 20% of the global population is afflicted by an allergic disease, with increasing incidence rates in both high- and low-income countries. The World Allergy Organization estimates that the total economic burden of asthma and allergic rhinitis alone is approximately $21 billion per year. While allergic stimuli are a complex and heterogenous class of inputs including parasites, pollens, food antigens, drugs, and metals, it has become clear that fungi are major drivers of allergic disease, with estimates that fungal sensitization occurs in 20–30% of atopic individuals and up to 80% of asthma patients. Fungi are eukaryotic microorganisms that can be found throughout the world in high abundance in both indoor and outdoor environments. Understanding how and why fungi act as triggers of allergic type 2 inflammation will be crucial for combating this important health problem. In recent years, there have been significant advances in our understanding of fungi-induced type 2 immunity, however there is still much we don’t understand, including why fungi have a tendency to induce allergic reactions in the first place. Here, we will discuss how fungi trigger type 2 immune responses and posit why this response has been evolutionarily selected for induction during fungal encounter.

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“…In contrast, Th17 cells are defined by RORγt expression and secrete IL-17, a cytokine that initiates neutrophil recruitment for phagocytosis of extracellular bacteria [23][24][25]. While Th1 and Th17 cells combat bacterial infections, Th2 cells express GATA3 and secrete cytokines that can coordinate mast cell and eosinophil defense against helminths [26]. Although this simple T helper framework allows a basic understanding of host responses to many pathogens, the exact module responsible for Chlamydia killing in the FRT has been difficult to identify.…”

Section: Introductionmentioning

confidence: 99%

Elimination of Chlamydia muridarum from the female reproductive tract is IL-12p40 dependent, but independent of Th1 and Th2 cells

Rixon,

Fong,

Morris

et al. 2024

PLoS Pathog

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Chlamydia vaccine approaches aspire to induce Th1 cells for optimal protection, despite the fact that there is no direct evidence demonstrating Th1-mediated Chlamydia clearance from the female reproductive tract (FRT). We recently reported that T-bet-deficient mice can resolve primary Chlamydia infection normally, undermining the potentially protective role of Th1 cells in Chlamydia immunity. Here, we show that T-bet-deficient mice develop robust Th17 responses and that mice deficient in Th17 cells exhibit delayed bacterial clearance, demonstrating that Chlamydia-specific Th17 cells represent an underappreciated protective population. Additionally, Th2-deficient mice competently clear cervicovaginal infection. Furthermore, we show that sensing of IFN-γ by non-hematopoietic cells is essential for Chlamydia immunity, yet bacterial clearance in the FRT does not require IFN-γ secretion by CD4 T cells. Despite the fact that Th1 cells are not necessary for Chlamydia clearance, protective immunity to Chlamydia is still dependent on MHC class-II-restricted CD4 T cells and IL-12p40. Together, these data point to IL-12p40-dependent CD4 effector maturation as essential for Chlamydia immunity, and Th17 cells to a lesser extent, yet neither Th1 nor Th2 cell development is critical. Future Chlamydia vaccination efforts will be more effective if they focus on induction of this protective CD4 T cell population.

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Modes of type 2 immune response initiation

Cited by 14 publications

References 70 publications

New developments in biotechnology applied to microorganisms

New developments in biotechnology applied to microorganisms

Novel mechanistic insights underlying fungal allergic inflammation

Elimination of Chlamydia muridarum from the female reproductive tract is IL-12p40 dependent, but independent of Th1 and Th2 cells

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