Immunization reveals a key role of Enterobacterial ClpB protein in the development of host anorexia
Anorexia nervosa (AN) is a psychiatric disease of unknown etiology. Recently, caseinolytic protease B (ClpB), produced by Enterobacteriaceae, was identified as an antigen mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. Here, we studied the role of ClpB in the development of activity-based anorexia (ABA), a rodent model of AN. In two series of ClpB immunization experiments, we show that when ClpB was lowered by antibodies, mice were protected against ABA, showing lean mass preservation, an increase in food intake, and reduced feeding anticipatory activity. On the contrary, if antibody production was accompanied by an increase of ClpB, ABA was aggravated. A key role of anti-ClpB IgG in ABA protection was confirmed in ClpB-tolerized mice and by IgG inhibiting ClpB- and α-MSH- activation of melanocortin 4 receptor. ClpB immunization influenced clpB DNA abundance in ABA mice without affecting fecal microbiota diversity and energy content. These data support a key role of Enterobacterial ClpB as well as its control by the immune system in host anorexia and provide background for ClpB immunoneutralization as a putative biotherapy of AN.
Authors
- Jérôme Leprince (ORCID: https://orcid.org/0000-0002-7814-9927)
- Jean‐Claude do Rego
- Sergueı̈ O. Fetissov (ORCID: https://orcid.org/0000-0002-2491-4945)
- John F. Baines (ORCID: https://orcid.org/0000-0002-8132-4909)
- Benjamin Lefranc (ORCID: https://orcid.org/0000-0002-0367-2414)
- Karthi Duraisamy (ORCID: https://orcid.org/0000-0001-5994-7133)
- Emilie Lahaye (ORCID: https://orcid.org/0000-0002-5785-5785)
- Nadia Andrea Andreani (ORCID: https://orcid.org/0000-0003-0330-9874)
- Jean‐Luc do Rego (ORCID: https://orcid.org/0009-0005-3526-1686)
- Astrid Dempfle (ORCID: https://orcid.org/0000-0002-2618-3920)
- Benjamin Thomas (ORCID: https://orcid.org/0009-0001-4078-209X)
- Lisa Wallart (ORCID: https://orcid.org/0009-0001-3788-0115)
- Philippe Chan (ORCID: https://orcid.org/0000-0001-6414-5581)
- Sophie Bernard (ORCID: https://orcid.org/0009-0006-1411-9231)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Différenciation et Communication Neuronale et Neuroendocrine (FR)
- University Hospital Schleswig-Holstein (DE)
- Institute for Research and Innovation in Biomedicine (FR)
- Max Planck Institute for Evolutionary Biology (DE)
- Université de Rouen Normandie (FR)
- University of Lübeck (DE)
Publication Details
- Journal
- Brain Behavior and Immunity
- Published
- 2025-10-23
- DOI
- https://doi.org/10.1016/j.bbi.2025.106152
- Citations
- 1
- Primary Topic
- Infant Health and Development
- Type
- article
- Field-Weighted Citation Impact
- 2.02