Persistence of Brucella abortus in the Bone Marrow of Infected Mice

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.

Omp25‐dependent engagement of SLAMF1 byBrucella abortusin dendritic cells limits acute inflammation and favours bacterial persistence in vivo

“…Immune modulation can thus be uncoupled from bacterial replication during acute infection. Brucella ‐targeting SLAMF1 may have broader consequences given that, on the one hand, Brucella colonising and persisting in murine bone marrow (Gutierrez‐Jimenez et al, ) is transmitted by bone marrow transplantation in humans (Naparstek, Block, & Slavin, ; Tuon, Gondolfo, & Cerchiari, ), and on the other hand, SLAMF1 is a key cell surface receptor of haematopoietic stem cells (Oguro, Ding, & Morrison, ). Investigating the impact of the Omp25‐dependent engagement of SLAMF1 on haematopoietic stem cell maintenance and differentiation along Brucella infection should open promising research avenues.…”

“…Immune modulation can thus be uncoupled from bacterial replication during acute infection. Brucella-targeting SLAMF1 may have broader consequences given that, on the one hand, Brucella colonising and persisting in murine bone marrow (Gutierrez-Jimenez et al, 2018) is transmitted by bone marrow transplantation in humans (Naparstek, Block, & Slavin, 1982;Tuon, Gondolfo, & Cerchiari, 2017), and on the other hand, SLAMF1 is a key cell surface receptor of haematopoietic stem cells (Oguro, Ding, & Morrison, 2013 Des Services Vétérinaires des Bouches du Rhône and the Regional Ethic Committee (authorization number 13.118). Authorisation of Brucella experimentation in BSL3 facility was given under the numbers: AMO-076712016-5, AMO-076712016-6, and AMO-076712016-7.…”

Neutrophils Dampen Adaptive Immunity in Brucellosis

“…We have used both the Genista and anti-PMN models to explore the role of PMNs and innate immune response during the onset of Brucella abortus infection (4, 15). Brucella organisms are intracellular stealth pathogens of animals and humans that avoid the activation of innate immunity, remaining in several tissues for protracted periods (15–17). B.…”

“…The course of human brucellosis parallels that observed in mice (16, 23). In the mouse model, brucellosis is divided into four phases according to the bacterial colonization of the target organs, the pathological signs, and the profile of the immune response (17, 23). The first phase corresponds to the onset of infection (also known as the incubation stage), which typically lasts 2 to 3 days.…”

Deletion of the transcriptional regulator GntR affects apoptosis and autophagy in Brucella abortus-infected RAW 264.7 cells

“…Macrophages, dendritic cells, and embryonic trophoblasts are the target cells of Brucella [3,4]. Furthermore, several other cells are susceptible to Brucella infection, and they include epithelial cells, human leukemic monocyte cells, osteoclasts, brain microvascular endothelial cells, and hepatic stellate cells [5][6][7][8]. Brucella can inhibit the maturation of phagosomes and prevent macrophages from forming phagolysosomes [9].…”