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Background  Inflammatory stimuli induce the hepatic iron regulatory hormone hepcidin, which contributes to anaemia of inflammation (AI). Hepcidin expression is regulated by the bone morphogenetic protein (BMP) and the interleukin-6 (IL-6) signalling pathways. Prior results indicate that the BMP type I receptor ALK3 is mainly involved in the acute inflammatory hepcidin induction four and 72 h after IL-6 administration. In this study, the role of ALK3 in a chronic model of inflammation was investigated. The intact, heat-killed bacterium  Brucella abortus  (BA) was used to analyse its effect on the development of inflammation and hypoferremia in mice with hepatocyte-specific  Alk3 -deficiency ( Alk3  fl/fl ;  Alb-Cre ) compared to control ( Alk3  fl/fl ) mice.    Results  An iron restricted diet prevented development of the iron overload phenotype in mice with hepatocyte-specific  Alk3  deficiency. Regular diet leads to iron overload and increased haemoglobin levels in these mice, which protects from the development of AI per se. Fourteen days after BA injection  Alk3  fl/fl ;  Alb-Cre  mice presented milder anaemia (Hb 16.7 g/dl to 11.6 g/dl) compared to  Alk3  fl/fl  control mice (Hb 14.9 g/dl to 8.6 g/dl). BA injection led to an intact inflammatory response in all groups of mice. In  Alk3  fl/fl ;  Alb-Cre  mice, SMAD1/5/8 phosphorylation was reduced after BA as well as after infection with  Staphylococcus aureus.  The reduction of the SMAD1/5/8 signalling pathway due to hepatocyte-specific  Alk3  deficiency partly suppressed the induction of STAT3 signalling.    Conclusion  The results reveal in vivo, that 1) hepatocyte-specific  Alk3  deficiency partly protects from AI, 2) the development of hypoferremia is partly dependent on ALK3, and 3) the ALK3/BMP/hepcidin axis may serve as a possible therapeutic target to attenuate AI.    Electronic supplementary material  The online version of this article (10.1186/s12899-018-0037-z) contains supplementary material, which is available to authorized users.

Deficiency of the BMP Type I receptor ALK3 partly protects mice from anemia of inflammation