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bioRxiv · 10.1101/2025.10.07.680913

Coxiella burnetii infects osteoclasts and alters their differentiation and function in a type IV secretion system-dependent manner

Lai, C.·Siddique, M. N. A. A.·Asghar, F.·Su, X.·Schulze-Luehrmann, J.·Jia, Y.·Escarrega, E. A.·Bozec, A.·Lang, R.·Luehrmann, A.·Soulat, D.
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Abstract

1Chronic Q fever is caused by persistent infection with the Gram-negative bacterium Coxiella burnetii. The mechanisms underlying this persistence remain elusive, but the presence of the bacteria in the bone marrow of C. burnetii-infected patients has been demonstrated. Therefore, we investigated the potential role of osteoclasts, the bone-resorbing cells, in harboring C. burnetii during the infection. The histological analysis of bones from a murine model of Q fever revealed the presence of C. burnetii inside osteoclasts. In vitro infection assays confirmed that osteoclasts can be infected with C. burnetii and supported bacterial replication in a type IVB secretion system (T4BSS)-dependent manner. Wild-type C. burnetii infection inhibited osteoclast differentiation and bone-resorbing activity, while the T4BSS mutant enhanced the differentiation and bone-degrading function of osteoclasts. Taken together, our findings identify osteoclasts as a potential host cell for C. burnetii, opening new perspectives on mechanisms that may underlie chronic Q fever. Additionally, infection-induced alterations in osteoclast function raise the possibility of alterations of the bone structure in affected patients.

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Lai, C., Siddique, M. N. A. A., Asghar, F., Su, X., Schulze-Luehrmann, J., Jia, Y., Escarrega, E. A., Bozec, A., Lang, R., Luehrmann, A., Soulat, D.. 2025-10-07. Coxiella burnetii infects osteoclasts and alters their differentiation and function in a type IV secretion system-dependent manner. https://doi.org/10.1101/2025.10.07.680913

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