RNAseqcharacterization ofB. burgdorferi-inducedinnate immune memoryandregulation ofLyme carditis through Acod1
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE236149 | GEO | 2023/11/01
REPOSITORIES: GEO
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Project description:Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and other less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound downregulation of mitochondrial components. We also characterize the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced IRF-4-dependent inflammatory responses. In vitro, glycolysis inhibition reduces the production of TNF by memory macrophages whereas in vivo, it produces the reversion of the Irf4-induced memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.
2021-09-09 | PXD019605 | Pride
Project description:Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and other less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound downregulation of mitochondrial components. We also characterize the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced IRF-4-dependent inflammatory responses. In vitro, glycolysis inhibition reduces the production of TNF by memory macrophages whereas in vivo, it produces the reversion of the Irf4-induced memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.
2020-12-22 | GSE152168 | GEO
Project description:Erythema migrans (EM) is a skin lesion caused by the spirochete B. burgdorferi (Bb) and is a hallmark initial sign of Lyme disease. Previous studies have demonstrated that T cells and innate immune cells mediate local inflammatory cytokine production that promote the reaction. Despite the established importance of B cells and antibodies in preventing Bb infection and resolving disease, the role of B cells in the skin immune response to Bb is incompletely defined. In this study, we characterized the immunophenotype of EM lesions and used single cell RNA-Seq to investigate B cell receptor (BCR) and T cell receptor (TCR) repertoires in the EM skin lesions and peripheral blood of patients with Lyme disease. We hypothesized that B cells from the circulation, potentially primed by exposure to Bb antigens in regional draining lymph nodes, are recruited into EM lesions and play an active role in the local response to infection. We found that B cells are more abundant in the EM lesion in comparison to autologous uninvolved skin and possess distinct characteristics, including abundant expression of MHCII genes and preferential IgM isotype usage. A subset exhibited low levels of somatic hypermutation despite a gene expression profile more consistent with memory than naïve B cell subsets. Moreover, infiltrating B cells were clonally expanded and a large fraction could be directly traced to circulating relatives. By leveraging single cell gene expression with paired BCR and TCR repertoire sequencing, we demonstrate, for the first time, that B cells are recruited to the skin infection site in early Lyme disease and express a phenotype suggesting that they could play a role in local antigen presentation and antibody production.
2021-06-07 | GSE171087 | GEO
Project description:Erythema migrans (EM) is a skin lesion caused by the spirochete B. burgdorferi (Bb) and is a hallmark initial sign of Lyme disease. Previous studies have demonstrated that T cells and innate immune cells mediate local inflammatory cytokine production that promote the reaction. Despite the established importance of B cells and antibodies in preventing Bb infection and resolving disease, the role of B cells in the skin immune response to Bb is incompletely defined. In this study, we characterized the immunophenotype of EM lesions and used single cell RNA-Seq to investigate B cell receptor (BCR) and T cell receptor (TCR) repertoires in the EM skin lesions and peripheral blood of patients with Lyme disease. We hypothesized that B cells from the circulation, potentially primed by exposure to Bb antigens in regional draining lymph nodes, are recruited into EM lesions and play an active role in the local response to infection. We found that B cells are more abundant in the EM lesion in comparison to autologous uninvolved skin and possess distinct characteristics, including abundant expression of MHCII genes and preferential IgM isotype usage. A subset exhibited low levels of somatic hypermutation despite a gene expression profile more consistent with memory than naïve B cell subsets. Moreover, infiltrating B cells were clonally expanded and a large fraction could be directly traced to circulating relatives. By leveraging single cell gene expression with paired BCR and TCR repertoire sequencing, we demonstrate, for the first time, that B cells are recruited to the skin infection site in early Lyme disease and express a phenotype suggesting that they could play a role in local antigen presentation and antibody production.
2021-06-07 | GSE169438 | GEO
Project description:Erythema migrans (EM) is a skin lesion caused by the spirochete B. burgdorferi (Bb) and is a hallmark initial sign of Lyme disease. Previous studies have demonstrated that T cells and innate immune cells mediate local inflammatory cytokine production that promote the reaction. Despite the established importance of B cells and antibodies in preventing Bb infection and resolving disease, the role of B cells in the skin immune response to Bb is incompletely defined. In this study, we characterized the immunophenotype of EM lesions and used single cell RNA-Seq to investigate B cell receptor (BCR) and T cell receptor (TCR) repertoires in the EM skin lesions and peripheral blood of patients with Lyme disease. We hypothesized that B cells from the circulation, potentially primed by exposure to Bb antigens in regional draining lymph nodes, are recruited into EM lesions and play an active role in the local response to infection. We found that B cells are more abundant in the EM lesion in comparison to autologous uninvolved skin and possess distinct characteristics, including abundant expression of MHCII genes and preferential IgM isotype usage. A subset exhibited low levels of somatic hypermutation despite a gene expression profile more consistent with memory than naïve B cell subsets. Moreover, infiltrating B cells were clonally expanded and a large fraction could be directly traced to circulating relatives. By leveraging single cell gene expression with paired BCR and TCR repertoire sequencing, we demonstrate, for the first time, that B cells are recruited to the skin infection site in early Lyme disease and express a phenotype suggesting that they could play a role in local antigen presentation and antibody production.
2021-06-07 | GSE169437 | GEO
Project description:Erythema migrans (EM) is a skin lesion caused by the spirochete B. burgdorferi (Bb) and is a hallmark initial sign of Lyme disease. Previous studies have demonstrated that T cells and innate immune cells mediate local inflammatory cytokine production that promote the reaction. Despite the established importance of B cells and antibodies in preventing Bb infection and resolving disease, the role of B cells in the skin immune response to Bb is incompletely defined. In this study, we characterized the immunophenotype of EM lesions and used single cell RNA-Seq to investigate B cell receptor (BCR) and T cell receptor (TCR) repertoires in the EM skin lesions and peripheral blood of patients with Lyme disease. We hypothesized that B cells from the circulation, potentially primed by exposure to Bb antigens in regional draining lymph nodes, are recruited into EM lesions and play an active role in the local response to infection. We found that B cells are more abundant in the EM lesion in comparison to autologous uninvolved skin and possess distinct characteristics, including abundant expression of MHCII genes and preferential IgM isotype usage. A subset exhibited low levels of somatic hypermutation despite a gene expression profile more consistent with memory than naïve B cell subsets. Moreover, infiltrating B cells were clonally expanded and a large fraction could be directly traced to circulating relatives. By leveraging single cell gene expression with paired BCR and TCR repertoire sequencing, we demonstrate, for the first time, that B cells are recruited to the skin infection site in early Lyme disease and express a phenotype suggesting that they could play a role in local antigen presentation and antibody production.
2021-06-07 | GSE172225 | GEO
Project description:Erythema migrans (EM) is a skin lesion caused by the spirochete B. burgdorferi (Bb) and is a hallmark initial sign of Lyme disease. Previous studies have demonstrated that T cells and innate immune cells mediate local inflammatory cytokine production that promote the reaction. Despite the established importance of B cells and antibodies in preventing Bb infection and resolving disease, the role of B cells in the skin immune response to Bb is incompletely defined. In this study, we characterized the immunophenotype of EM lesions and used single cell RNA-Seq to investigate B cell receptor (BCR) and T cell receptor (TCR) repertoires in the EM skin lesions and peripheral blood of patients with Lyme disease. We hypothesized that B cells from the circulation, potentially primed by exposure to Bb antigens in regional draining lymph nodes, are recruited into EM lesions and play an active role in the local response to infection. We found that B cells are more abundant in the EM lesion in comparison to autologous uninvolved skin and possess distinct characteristics, including abundant expression of MHCII genes and preferential IgM isotype usage. A subset exhibited low levels of somatic hypermutation despite a gene expression profile more consistent with memory than naïve B cell subsets. Moreover, infiltrating B cells were clonally expanded and a large fraction could be directly traced to circulating relatives. By leveraging single cell gene expression with paired BCR and TCR repertoire sequencing, we demonstrate, for the first time, that B cells are recruited to the skin infection site in early Lyme disease and express a phenotype suggesting that they could play a role in local antigen presentation and antibody production.
2021-06-07 | GSE171215 | GEO
Project description:Erythema migrans (EM) is a skin lesion caused by the spirochete B. burgdorferi (Bb) and is a hallmark initial sign of Lyme disease. Previous studies have demonstrated that T cells and innate immune cells mediate local inflammatory cytokine production that promote the reaction. Despite the established importance of B cells and antibodies in preventing Bb infection and resolving disease, the role of B cells in the skin immune response to Bb is incompletely defined. In this study, we characterized the immunophenotype of EM lesions and used single cell RNA-Seq to investigate B cell receptor (BCR) and T cell receptor (TCR) repertoires in the EM skin lesions and peripheral blood of patients with Lyme disease. We hypothesized that B cells from the circulation, potentially primed by exposure to Bb antigens in regional draining lymph nodes, are recruited into EM lesions and play an active role in the local response to infection. We found that B cells are more abundant in the EM lesion in comparison to autologous uninvolved skin and possess distinct characteristics, including abundant expression of MHCII genes and preferential IgM isotype usage. A subset exhibited low levels of somatic hypermutation despite a gene expression profile more consistent with memory than naïve B cell subsets. Moreover, infiltrating B cells were clonally expanded and a large fraction could be directly traced to circulating relatives. By leveraging single cell gene expression with paired BCR and TCR repertoire sequencing, we demonstrate, for the first time, that B cells are recruited to the skin infection site in early Lyme disease and express a phenotype suggesting that they could play a role in local antigen presentation and antibody production.
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2021-08-27 | GSE153376 | GEO