Abstract

Brucellosis is a zoonotic bacterial infection that may persist for long periods causing relapses in antibiotic-treated patients. The ability of Brucella to develop chronic infections is linked to their capacity to invade and replicate within the mononuclear phagocyte system, including the bone marrow (BM). Persistence of Brucella in the BM has been associated with hematological complications such as neutropenia, thrombocytopenia, anemia, and pancytopenia in human patients. In the mouse model, we observed that the number of Brucella abortus in the BM remained constant for up to 168 days of postinfection. This persistence was associated with histopathological changes, accompanied by augmented numbers of BM myeloid GMP progenitors, PMNs, and CD4+ lymphocytes during the acute phase (eight days) of the infection in the BM. Monocytes, PMNs, and GMP cells were identified as the cells harboring Brucella in the BM. We propose that the BM is an essential niche for the bacterium to establish long-lasting infections and that infected PMNs may serve as vehicles for dispersion of Brucella organisms, following the Trojan horse hypothesis. Monocytes are solid candidates for Brucella reservoirs in the BM.

Highlights

  • Brucellosis is a zoonotic bacterial infection caused by members of the genus Brucella [1]

  • The ability of Brucella organisms to develop chronic infections is linked to their competence to invade the mononuclear phagocyte system, where they replicate within the endoplasmic reticulum [6]

  • B. abortus colony forming units (CFU) counting was performed from the spleen, lymph nodes, and bone marrow (BM) during the lapse of 168 days of postinfection (Figure 1(a))

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Summary

Introduction

Brucellosis is a zoonotic bacterial infection caused by members of the genus Brucella [1]. The disease is long-lasting, displaying a variety of clinical and pathological manifestations that may persist for months or years [2,3,4,5]. If the infection is not properly treated, it may cause death. The ability of Brucella organisms to develop chronic infections is linked to their competence to invade the mononuclear phagocyte system, where they replicate within the endoplasmic reticulum [6]. The bacterium is isolated from the BM in about half of the human patients with brucellosis [4]. In all brucellosis cases, the BM displays histopathological alterations, whether or not the bacterium is isolated from this tissue. Common hematological signs are neutropenia, thrombocytopenia, and anemia, and in severe cases, pancytopenia has been

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