Comprehensive Mapping of the Cell Response to Borrelia bavariensis in the Brain Microvascular Endothelial Cells in vitro Using RNA-Seq

Tkáčová, Zuzana; Bhide, Katarína; Mochnáčová, Evelína; Petroušková, Patrícia; Hruškovicová, Jana; Kulkarni, Amod; Bhide, Mangesh

doi:10.3389/fmicb.2021.760627

Cited by 7 publications

(8 citation statements)

References 83 publications

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“…However, only 5 PPR-related genes were found to be differentially expressed ( Figure 6 ), namely TLR2, NOD2, and COLEC12 (receptors), TRIL (the modulator of TLR3/4 signaling), and TICAM-1 (the adaptor molecule of TLR3 signaling). In contrast to previous findings ( Káňová et al., 2019 ; Tkáčová et al., 2021 ), the TLR2 adaptor molecule MyD88 and the transcription regulator NFĸB were not found to be significantly expressed in the current study. The inclusion of pericytes and astrocytes in this study, as opposed to only hBMECs in previous studies, may explain the variation.…”

Section: Discussioncontrasting

confidence: 99%

“…The Cross talk includes ligand-receptor interactions, cell signaling, host cell responses to resist pathogen invasion, etc. ( Kánová et al., 2018 ; Káňová et al., 2019 ; Thompson et al., 2020 ; Tkáčová et al., 2020 ; Tkáčová et al., 2021 ). Earlier studies describing the BBB response to invading neuropathogens have focused on BMECs, the barrier’s frontline cells.…”

Section: Discussionmentioning

confidence: 99%

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Differential transcriptome response of blood brain barrier spheroids to neuroinvasive Neisseria and Borrelia

Kulkarni,

Jozefiaková,

Bhide

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundThe blood-brain barrier (BBB), a highly regulated interface between the blood and the brain, prevents blood-borne substances and pathogens from entering the CNS. Nevertheless, pathogens like Neisseria meningitidis and Borrelia bavariensis can breach the BBB and infect the brain parenchyma. The self-assembling BBB-spheroids can simulate the cross talk occurring between the cells of the barrier and neuroinvasive pathogens.MethodsBBB spheroids were generated by co-culturing human brain microvascular endothelial cells (hBMECs), pericytes and astrocytes. The BBB attributes of spheroids were confirmed by mapping the localization of cells, observing permeability of angiopep2 and non-permeability of dextran. Fluorescent Neisseria, Borrelia or E. coli (non-neuroinvasive) were incubated with spheroids to observe the adherence, invasion and spheroid integrity. Transcriptome analysis with NGS was employed to investigate the response of BBB cells to infections.ResultshBMECs were localized throughout the spheroids, whereas pericytes and astrocytes were concentrated around the core. Within 1 hr of exposure, Neisseria and Borrelia adhered to spheroids, and their microcolonization increased from 5 to 24 hrs. Integrity of spheroids was compromised by both Neisseria and Borrelia, but not by E. coli infection. Transcriptome analysis revealed a significant change in the expression of 781 genes (467 up and 314 down regulated) in spheroids infected with Neisseria, while Borrelia altered the expression of 621 genes (225 up and 396 down regulated). The differentially expressed genes could be clustered into various biological pathways like cell adhesion, extracellular matrix related, metallothionines, members of TGF beta, WNT signaling, and immune response. Among the differentially expressed genes, 455 (48%) genes were inversely expressed during Neisseria and Borrelia infection.ConclusionThe self-assembling spheroids were used to perceive the BBB response to neuroinvasive pathogens - Neisseria and Borrelia. Compromised integrity of spheroids during Neisseria and Borrelia infection as opposed to its intactness and non-adherence of E. coli (non-neuroinvasive) denotes the pathogen dependent fate of BBB. Genes categorized into various biological functions indicated weakened barrier properties of BBB and heightened innate immune response. Inverse expression of 48% genes commonly identified during Neisseria and Borrelia infection exemplifies unique response of BBB to varying neuropathogens.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differential transcriptome response of blood brain barrier spheroids to neuroinvasive Neisseria and Borrelia

Kulkarni,

Jozefiaková,

Bhide

et al. 2023

Front. Cell. Infect. Microbiol.

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“…The study concluded that abnormal serum antibody indices and elevated levels of CXCL8 and CXCL10 indicated a potential connection to Borrelia-mediated inflammation [ 40 ]. A similar upregulation was observed in human brain microvascular endothelial cells (hBMECs) infected with Borrelia bavariensis , wherein CXCL8 and CXCL10 were significantly elevated, correlating with cellular stress and the innate immune response [ 41 ].…”

Section: Discussionmentioning

confidence: 74%

“…Gene ontology analysis of these markers revealed signaling cascades associated with cell communication, organization of the extracellular matrix, cellular responses triggered by pattern recognition receptors, and antigen processing. These pathways suggest potential mechanisms exploited by B. burgdorferi to traverse the blood-brain barrier (BBB) [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Evidence for the presence of Borrelia burgdorferi in invasive breast cancer tissues

Patel,

Thippani,

Jathan

et al. 2024

EuJMI

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Borrelia burgdorferi, the causative agent of Lyme disease, has recently been demonstrated to infect and enhance the invasive properties of breast cancer cells, while also influencing the expression of inflammatory chemokines (CXCL8 and CXCL10). This study investigates the presence of B. burgdorferi in invasive breast cancer tissues using commercially available, FDA-approved breast cancer tissue microarrays consisting of 350 ductal, 32 lobular, and 22 intraductal invasive breast carcinomas, alongside 29 normal breast tissues. Employing fluorescent immunohistochemical staining and high-resolution imaging, the findings revealed that approximately 20% of invasive lobular and ductal carcinomas, followed by 14% of intraductal carcinomas, tested positive for B. burgdorferi, while all normal breast tissues tested negative. PCR analysis further confirmed the presence of B. burgdorferi DNA in breast cancer tissues. Moreover, 25% of B. burgdorferi-positive tissues exhibited expression of both chemokines, CXCL8 and CXCL10, which was not observed in B. burgdorferi-negative tissues. Analysis of available patient data, including age, indicated a correlation between older patients and B. burgdorferi-positive tissues. This study validates the presence of B. burgdorferi in invasive breast cancer tissues and highlights the involvement of key CXCL family members associated with inflammatory processes.

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“…burgdorferi -dependent reduction. Interestingly, a recent in vitro study of neuroborreliosis, using human brain microvascular endothelial cells challenged with Borrelia bavariensis , also showed an upregulation of IRAK2 and MYD88 , while no significant changes were detected for IRAK1 or TRAF6 expression [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Borrelia burgdorferi-mediated induction of miR146a-5p fine tunes the inflammatory response in human dermal fibroblasts

et al. 2023

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Colonization of a localized area of human skin by Borrelia burgdorferi after a bite from an infected tick is the first step in the development of Lyme disease. The initial interaction between the pathogen and the human host cells is suggested to impact later outcomes of the infection. MicroRNAs (miRNAs) are well known to be important regulators of host inflammatory and immune responses. While miRNAs have been shown to play a role in the inflammatory response to B. burgdorferi at late stages of infection in the joints, the contributions of miRNAs to early B. burgdorferi infection have yet to be explored. To address this knowledge gap, we used the published host transcriptional responses to B. burgdorferi in erythema migrans skin lesions of early Lyme disease patients and a human dermal fibroblasts (HDFs)/B. burgdorferi co-culture model to predict putative upstream regulator miRNAs. This analysis predicted a role for miR146a-5p in both, B. burgdorferi-infected skin and -stimulated HDFs. miR146a-5p was confirmed to be significantly upregulated in HDF stimulated with B. burgdorferi for 24 hours compared to uninfected control cells. Furthermore, manipulation of miR146a-5p expression (overexpression or inhibition) altered the B. burgdorferi driven inflammatory profile of HDF cells. Our results suggest that miR146a-5p is an important upstream regulator of the transcriptional and immune early response to early B. burgdorferi infection.

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Comprehensive Mapping of the Cell Response to Borrelia bavariensis in the Brain Microvascular Endothelial Cells in vitro Using RNA-Seq

Cited by 7 publications

References 83 publications

Differential transcriptome response of blood brain barrier spheroids to neuroinvasive Neisseria and Borrelia

Differential transcriptome response of blood brain barrier spheroids to neuroinvasive Neisseria and Borrelia

Evidence for the presence of Borrelia burgdorferi in invasive breast cancer tissues

Borrelia burgdorferi-mediated induction of miR146a-5p fine tunes the inflammatory response in human dermal fibroblasts

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