NLRP3 promotes allergic responses to birch pollen extract in a model of intranasal sensitization

Front Immunol. 2024 Jun 12:15:1393819. doi: 10.3389/fimmu.2024.1393819. eCollection 2024.

Abstract

Introduction & objective: Allergic sensitization is an essential step in the development of allergic airway inflammation to birch pollen (BP); however, this process remains to be fully elucidated. Recent scientific advances have highlighted the importance of the allergen context. In this regard, microbial patterns (PAMPs) present on BP have attracted increasing interest. As these PAMPs are recognized by specialized pattern recognition receptors (PRRs), this study aims at investigating the roles of intracellular PRRs and the inflammasome regulator NLRP3.

Methods: We established a physiologically relevant intranasal and adjuvant-free sensitization procedure to study BP-induced systemic and local lung inflammation.

Results: Strikingly, BP-sensitized Nlrp3-deficient mice showed significantly lower IgE levels, Th2-associated cytokines, cell infiltration into the lung, mucin production and epithelial thickening than their wild-type counterparts, which appears to be independent of inflammasome formation. Intriguingly, bone-marrow chimera revealed that expression of NLRP3 in the hematopoietic system is required to trigger an allergic response.

Conclusion: Overall, this study identifies NLRP3 as an important driver of BP-induced allergic immune responses.

Keywords: NLR; NLRP3; birch pollen allergy; inflammasome; intranasal sensitization.

MeSH terms

  • Administration, Intranasal*
  • Allergens* / immunology
  • Animals
  • Betula* / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Hypersensitivity / immunology
  • Immunoglobulin E / immunology
  • Inflammasomes / immunology
  • Inflammasomes / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout*
  • NLR Family, Pyrin Domain-Containing 3 Protein* / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein* / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Plant Extracts / pharmacology
  • Pollen* / immunology

Substances

  • Allergens
  • Cytokines
  • Immunoglobulin E
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Plant Extracts

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the doctoral college “immunity in cancer and allergy” (ICA) by the Austrian science fund FWF [grant DOI: 10.55776/W1213]. For open access purposes, the author has applied a CC BY public copyright license to any author accepted manuscript version arising from this submission.