Mycobacterium tuberculosis escapes from the phagosomes of infected human osteoclasts reprograms osteoclast development via dysregulation of cytokines and chemokines. Issue 1 (10th September 2013)

• Record Type: Journal Article
• Authors: Hoshino, Akiyoshi; Hanada, Sanshiro; Yamada, Hiroyuki; Mii, Shinji; Takahashi, Masahide; Mitarai, Satoshi; Yamamoto, Kenji; Manome, Yoshinobu
• Is Part Of: Pathogens and disease. Volume 70:Issue 1(2014:Feb.)
• Page Start: 28
• Page End: 39
• Publication Date: 2013-09-10
• Subjects: Medical microbiology -- Periodicals; Pathogenic microorganisms -- Periodicals; Communicable diseases -- Microbiology -- Periodicals; Communicable diseases -- Pathogenesis -- Periodicals; Host-parasite relationships -- Periodicals; Systems biology -- Periodicals; 616.904105
• DOI: 10.1111/2049-632X.12082
• Languages: English
• ISSNs: 2049-632X

Abstract

<abstract abstract-type="main" id="fim12082-abs-0001"> <title>Abstract</title> <p>Spinal tuberculosis is a condition characterized by massive resorption of the spinal vertebrae due to the infection with <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>). 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 <italic>Mtb</italic> strain. We found that the intracellular <italic>Mtb</italic> infection of multinuclear osteoclasts resulted in the rapid growth of <italic>Mtb</italic> and an osteolytic response, rather than inflammation. In response to <italic>Mtb</italic> 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 <italic>Mtb</italic> 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 <italic>Mtb</italic> strain resulted in diminished production of these chemokines. These findings indicate that intracellular <italic>Mtb</italic> infection in multinuclear osteoclasts reprograms osteoclast development via the dysregulation of cytokines and chemokines.</p> </abstract>