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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1428079

Neutrophil-activating protein (NAP) in Bacillus spores inhibits casein allergy via TLR2 signaling

Provisionally accepted
Liang Zhuwei Liang Zhuwei 1Chao Zhang Chao Zhang 2Xiaoyu Liu Xiaoyu Liu 3Kaiyue Yang Kaiyue Yang 1Zhile Xiong Zhile Xiong 1Bingshao Liang Bingshao Liang 4Jialiang Mai Jialiang Mai 5Xiaojun Xiao Xiaojun Xiao 3Jie Liu Jie Liu 3Ping-Chang Yang Ping-Chang Yang 3Damo Xu Damo Xu 3*Zhenwen Zhou Zhenwen Zhou 1*
  • 1 Shenzhen Longgang District Maternal and Child Health Care Hospital, Shenzhen, China
  • 2 Beijing Chest Hospital, Capital Medical University, Beijing, Beijing Municipality, China
  • 3 Shenzhen University, Shenzhen, Guangdong Province, China
  • 4 Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
  • 5 Foshan Women and Children Hospital, Foshan, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Background: Milk allergy commonly occurs in children, mainly caused by bovine-derived casein (CAS) protein. Neutrophil-activating protein (NAP) of Helicobacter pylori plays an immunomodulatory role with potential to suppress Th2-type immune responses. Bacillus subtilis (B. subtilis) spores are commonly used as oral vectors for drug delivery. Objective: To investigate whether recombinantly expressed NAP on B. subtilis spores could be an effective treatment for CAS allergy in mouse. Methods: After CAS sensitization, mice were orally administered B. subtilis spores expressing recombinant NAP for 6 weeks. Allergic symptoms and parameters were evaluated after CAS challenge oral gavage, including allergic inflammation, splenic cytokines, and serum-specific antibodies. Protein levels of Toll-like receptor 2 (TLR2) and c-JUN in the jejunum tissue were measured by western blot. Bone marrow-derived macrophages (BMDMs) were stimulated with inactivated NAP spores to measure the influence on cytokine profiles in vitro. Results: NAP recombinant spore treatment significantly reduced allergic symptoms and intestinal inflammation. Interleukin-12 and interferon-gamma levels increased, whereas serum CAS-specific IgG1 and IgE levels decreased. TLR2 and c-JUN expression levels were elevated in the jejunal tissue. Inactivated NAP spores polarized BMDMs to the M1 phenotype and enhanced cytokine expression, which were inhibited by a TLR2 neutralizing antibody. Conclusion: NAP offers a new strategy in the treatment of CAS allergy by inhibiting the Th2 response, while eliciting macrophages to promote Th1 immune responses.

    Keywords: B. subtilis spores, Casein allergy, Neutrophil-activating protein, Toll-Like Receptor 2, oral immunotherapy

    Received: 05 May 2024; Accepted: 10 Oct 2024.

    Copyright: © 2024 Zhuwei, Zhang, Liu, Yang, Xiong, Liang, Mai, Xiao, Liu, Yang, Xu and Zhou. 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:
    Damo Xu, Shenzhen University, Shenzhen, 518060, Guangdong Province, China
    Zhenwen Zhou, Shenzhen Longgang District Maternal and Child Health Care Hospital, Shenzhen, China

    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.