Spinal tuberculosis is a condition characterized by massive resorption of the spinal vertebrae due to the
infection with Mycobacterium tuberculosis (Mtb). However, the pathogenesis of
spinal tuberculosis has not been established because it was almost completely eradicated by the establishment of
antibiotic treatment in the mid-20th century. In this study, we investigated the inflammatory responses of human multinucleated osteoclasts infected with virulent Mtb strain. We found that the intracellular Mtb
infection of multinuclear osteoclasts resulted in the rapid growth of Mtb and an osteolytic response, rather than
inflammation. In response to Mtb
infection, the mononuclear osteoclast precursors produced proinflammatory
cytokines including
tumor necrosis factor (TNF)-α, an intrinsic characteristic they share with macrophages. In contrast, highly fused multinucleated osteoclasts incapacitated the production of these
cytokines. Instead, the intracellular Mtb inside multinuclear osteoclasts escaped from the endosome/phagosome, leading to a different pattern of osteoclast activation, with the production of
chemokines such as CCL5, CCL17, CCL20, CCL22, CCL24, and CCL25. Moreover, intracellular
infection with an avirulent Mtb strain resulted in diminished production of these
chemokines. These findings indicate that intracellular Mtb
infection in multinuclear osteoclasts reprograms osteoclast development via the dysregulation of
cytokines and
chemokines.