Chronic Systemic Infection of Mice with Leishmania infantum Leads to Increased Bone Mass

Lai C, Heinemann J, Schleicher U, Schett G, Bogdan C, Bozec A, Soulat D (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Journal of Bone and Mineral Research American Society for Bone and Mineral Research

Abstract

Vector-borne infections of humans with the protozoan parasite Leishmania (L.) infantum can cause a systemic and potentially lethal disease termed visceral leishmaniasis. 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-derived 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. (c) 2022 American Society for Bone and Mineral Research (ASBMR).

Authors with CRIS profile

Chaobo Lai Professur für Experimentelle Immuntherapie Jennifer Heinemann Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Ulrike Schleicher Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Georg Schett Lehrstuhl für Innere Medizin III Christian Bogdan Lehrstuhl für Mikrobiologie und Infektionsimmunologie Aline Bozec Juniorprofessur für Osteoimmunologie Didier Soulat Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

How to cite

APA:

Lai, C., Heinemann, J., Schleicher, U., Schett, G., Bogdan, C., Bozec, A., & Soulat, D. (2022). Chronic Systemic Infection of Mice with Leishmania infantum Leads to Increased Bone Mass. Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.4733

MLA:

Lai, Chaobo, et al. "Chronic Systemic Infection of Mice with Leishmania infantum Leads to Increased Bone Mass." Journal of Bone and Mineral Research (2022).

BibTeX: Download