Immunization reveals a key role of Enterobacterial ClpB protein in the development of host anorexia

Abstract

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.

Keywords: Adaptive immunity; Animal models; Appetite; Autoantibodies; ClpB; Enterobacteriaceae; Gut microbiota-brain axis; Neuropeptides.