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In the corresponding mouse model, an intravenous infection with L. infantum leads to the persistence of parasites in various organs, including bone marrow (BM). Considering the anatomical proximity between the BM and the cortical bone, we investigated whether a chronic infection with L. infantum affected bone homeostasis. Unexpectedly, chronic infection with L. infantum caused an increase in bone mass in mice. In vivo, an increased number of osteoblasts and osteocytes and a decreased maturation of osteoclasts characterized the phenotype. Confocal laser scanning fluorescence microscopy confirmed the infection of BM macrophages but also revealed the presence of parasites in osteoclasts. In vitro, mature osteoclasts took up L. infantum parasites. However, infection of osteoclast progenitors abolished their differentiation and function. In addition, secretory products of infected BM\u2013derived macrophages inhibited the maturation of osteoclasts. Both in vitro and in vivo, infected macrophages and osteoclasts showed an enhanced expression of the anti-osteoclastogenic chemokine CCL5 (RANTES). Neutralization of CCL5 prevented the inhibition of osteoclast generation seen in the presence of culture supernatants from L. infantum-infected macrophages. Altogether, our study shows that chronic infection with Leishmania increases bone mass by inducing bone formation and impairing osteoclast differentiation and function. \u00a9 2022 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4733","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T14:17:00Z","timestamp":1667571420000},"page":"86-102","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic Systemic Infection of Mice with Leishmania infantum Leads to Increased Bone Mass"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0703-5815","authenticated-orcid":false,"given":"Chaobo","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Internal Medicine 3, Rheumatology and Immunology Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t (FAU) Erlangen-N\u00fcrnberg Erlangen Germany"},{"name":"Mikrobiologisches Institut\u2014Klinische Mikrobiologie, Immunologie und Hygiene Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t (FAU) Erlangen-N\u00fcrnberg Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Heinemann","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut\u2014Klinische Mikrobiologie, Immunologie und Hygiene Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t (FAU) Erlangen-N\u00fcrnberg Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Schleicher","sequence":"additional","affiliation":[{"name":"Medical Immunology Campus Erlangen FAU Erlangen-N\u00fcrnberg Erlangen Germany"},{"name":"Mikrobiologisches Institut\u2014Klinische Mikrobiologie, Immunologie und Hygiene Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t (FAU) Erlangen-N\u00fcrnberg Erlangen 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