Brucella abortus-Stimulated Platelets Activate Brain Microvascular Endothelial Cells Increasing Cell Transmigration through the Erk1/2 Pathway

Rodrı́guez, Ana; Trotta, Aldana; Melnyczajko, Agustina P.; Miraglia, María Cruz; Kim, Kwang Sik; Delpino, M. Victoria; Barrionuevo, Paula; Giambartolomei, Guillermo H.

doi:10.3390/pathogens9090708

Cited by 7 publications

(4 citation statements)

References 49 publications

(80 reference statements)

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“…The entry of B. abortus to the brain parenchyma takes place within infected monocytes as a Trojan horse after peripheral inflammation of the blood-brain barrier induced by the bacterium ( 31 , 40 ). In turn, these infected monocytes served as bacterial sources for de novo infection for astrocytes and microglia ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

“…releases outer-membrane vesicles (OMVs) containing lipopolysaccharide (LPS), outer membrane proteins, and other bacterial components (30). To rule out the possibility that the remaining OMVs present in SN after astrocyte infection were i m p l i c a t e d i n m i c r o g l i a a c t i v a t i o n , w e p e r f o r m e d ultracentrifugation of SN, as previously described (30,31). Cocultures were then incubated with OMV-free SN for 48 h and neuronal death was evaluated.…”

Section: Culture Supernatants From B Abortusinfected Astrocytes Induc...mentioning

confidence: 99%

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Bystander activation of microglia by Brucella abortus-infected astrocytes induces neuronal death via IL-6 trans-signaling

Rodríguez,

De Santis Arévalo,

Dennis

et al. 2024

Front. Immunol.

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Inflammation plays a key role in the pathogenesis of neurobrucellosis where glial cell interactions are at the root of this pathological condition. In this study, we present evidence indicating that soluble factors secreted by Brucella abortus-infected astrocytes activate microglia to induce neuronal death. Culture supernatants (SN) from B. abortus-infected astrocytes induce the release of pro-inflammatory mediators and the increase of the microglial phagocytic capacity, which are two key features in the execution of live neurons by primary phagocytosis, a recently described mechanism whereby B. abortus-activated microglia kills neurons by phagocytosing them. IL-6 neutralization completely abrogates neuronal loss. IL-6 is solely involved in increasing the phagocytic capacity of activated microglia as induced by SN from B. abortus-infected astrocytes and does not participate in their inflammatory activation. Both autocrine microglia-derived and paracrine astrocyte-secreted IL-6 endow microglial cells with up-regulated phagocytic capacity that allows them to phagocytose neurons. Blocking of IL-6 signaling by soluble gp130 abrogates microglial phagocytosis and concomitant neuronal death, indicating that IL-6 activates microglia via trans-signaling. Altogether, these results demonstrate that soluble factors secreted by B. abortus-infected astrocytes activate microglia to induce, via IL-6 trans-signaling, the death of neurons. IL-6 signaling inhibition may thus be considered a strategy to control inflammation and CNS damage in neurobrucellosis.

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Section: Discussionmentioning

confidence: 99%

Section: Culture Supernatants From B Abortusinfected Astrocytes Induc...mentioning

confidence: 99%

Bystander activation of microglia by Brucella abortus-infected astrocytes induces neuronal death via IL-6 trans-signaling

Rodríguez,

De Santis Arévalo,

Dennis

et al. 2024

Front. Immunol.

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“…This process may lead to intracranial in ammation, ultimately causing corresponding neurological de cits. However, it's important to note that the exact mechanisms and interactions involved in this process are still subject to ongoing research and investigation [10]. Additionally, some studies have proposed that Brucellosis may lead to the corresponding clinical manifestations by directly releasing endotoxins, which can cause damage to neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

Characterization of 38 cases of Neurobrucellosis

Qi,

Niu,

Ren

et al. 2024

Preprint

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Aim：In this study, we thoroughly examine and discuss the clinical features, laboratory findings, treatment, and recovery of 38 neurobrucellosis cases. Additionally, we provide insights into the most recent research advances in the field of neurobrucellosis. Materials and methods：In this study, we collected general data, clinical characteristics, ancillary tests, and treatment plans of 38 cases of neurobrucellosis diagnosed and treated at the General Hospital of Ningxia Medical University from March 2012 to December 2022. Results：Among the 38 cases, 25 were male, and 23 had a clear history of cattle and sheep exposure. The most common clinical manifestations were fever (81.58%) and headache (76.32%). Brucella agglutination test was positive in 37 patients, and 37 patients showed increased protein in the cerebrospinal fluid. All 38 patients had a complete blood routine, with 11 cases showing abnormal white blood cell counts. Among the 29 patients who underwent cranial magnetic resonance imaging, 12 showed abnormalities. There were no in-hospital deaths among the patients. Conclusions：Neurobrucellosis exhibits diverse clinical manifestations and can be difficult to differentiate from tuberculous meningitis. Routine tests such as complete blood routine and cranial magnetic resonance imaging have limited diagnostic value for neurobrucellosis and are prone to clinical misdiagnosis and underdiagnosis. Patients with a history of contact with cattle and sheep in nearby grazing areas and presenting with symptoms such as fever and headache should undergo laboratory tests such as Brucella agglutination test or cerebrospinal fluid culture to establish an early and accurate diagnosis. Prompt initiation of treatment with doxycycline, rifampin, and ceftriaxone sodium triple therapy against Brucellosis is crucial in areas close to pastoral regions with potential cattle and sheep exposure.

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“…Regardless of the mechanism, it is clear that once the bacterium reaches the CNS it induces a pathological pro-inflammatory response. The study of Rodriguez et al [ 13 ] investigated the role of Brucella abortus -stimulated platelets on human brain microvascular endothelial cell (HBMEC) activation. Platelets enhanced HBMEC activation in response to B. abortus infection.…”

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confidence: 99%