94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cellular Biochemistry
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1533742
This article is part of the Research TopicUnraveling the Role of Protein Modifications in Tumor Dynamics and Immune ModulationView all 3 articles
rFIP-nha activates macrophages towards a pro-inflammatory phenotype via AIM2 inflammasome modulation
Provisionally accepted- 1Wageningen University and Research, Wageningen, Netherlands
- 2Wageningen Food & Biobased Research, Wageningen University and Research, Wageningen, Netherlands
- 3Chinese Academy of Agricultural Sciences (CAAS), Beijing, Beijing Municipality, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Fungal immunomodulatory proteins (FIPs) are small proteins from fungi with considerable immunomodulatory activity. FIP-nha (Nectria haematococca) contains two glycosylation sites at positions N5 and N39, and displays a high thermostability and notable anti-tumour activity. However, FIP-nha's immunomodulatory activity on macrophages and the associated mechanism remain unclear. In this study, three rFIP-nha glycan mutants (N5A, N39A, N5+39A) were recombinantly expressed in Pichia pastoris. To test the impact on FIP-nha's immunomodulatory activity, the phagocytotic activity, cytokine secretion, and gene expression of THP-1 macrophages were investigated. rFIP-nha and its mutants reduced macrophage phagocytosis, and induced IL-1β, IL-12 and IL-10 cytokine secretion significantly, indicating that the protein confers a pro-inflammatory behaviour on THP-1 macrophages. However, there were no obvious differences among the different glycan mutants, indicating that the observed activation mechanisms are likely glycosylation-independent. Furthermore, to study the immunomodulatory mechanism, four kinds of inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2) were tested at transcriptional level. AIM2 was found to be 10-fold up-regulated. Then, THP1-KO-ASC cells and AIM2 related inhibitors showed that IL-1β release induced by rFIP-nha is ASC signalling pathway dependent. Taken together, these findings suggest that rFIP-nha activates THP-1 macrophages in a pro-inflammatory way by activating the AIM2 inflammasome.
Keywords: Immunomodulatory protein, macrophage, pro-inflammatory, IL-1β, AIM2 inflammasome, Glycosylation
Received: 25 Nov 2024; Accepted: 14 Apr 2025.
Copyright: © 2025 Liu, Li, Wichers, Bastiaan-Net and Hoppenbrouwers. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yusi Liu, Wageningen University and Research, Wageningen, Netherlands
Shanna Bastiaan-Net, Wageningen Food & Biobased Research, Wageningen University and Research, Wageningen, 6708, Netherlands
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.