Infection of Monocytes From Tuberculosis Patients With Two Virulent Clinical Isolates of Mycobacterium tuberculosis Induces Alterations in Myeloid Effector Functions

Lavalett, Lelia; Ortega, Héctor; Barrera, Luis F.

doi:10.3389/fcimb.2020.00163

Cited by 11 publications

(12 citation statements)

References 95 publications

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“…Using the dual RNA-seq approach, we profiled the transcriptomic cross-talk between human splenic macrophages (hSMs) infected with two clinical isolates of the Latin American and Mediterranean (LAM) family of Mtb UT127 and UT-205. Our previous genomic characterization of those isolates demonstrated that the strains are highly genetically similar (99.6%) [22,33]; however, evidence that they induce a different pattern of cell death in human alveolar and monocyte-derived macrophages [34] and a distinct transcriptomic response in human alveolar and splenic macrophages [35] led us to the hypothesis that these clinical strains drive very different host responses to infection. Indeed, there was a more robust innate immune response to UT127 clinical isolate, suggesting an early and more potent recognition by the innate immune system than the UT205 strain, which may have consequences in the progression of the disease.…”

Section: Introductionmentioning

confidence: 99%

Dual RNA Sequencing of Mycobacterium tuberculosis-Infected Human Splenic Macrophages Reveals a Strain-Dependent Host–Pathogen Response to Infection

López-Agudelo

Baena

Barrera

et al. 2022

IJMS

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Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), leading to pulmonary and extrapulmonary TB, whereby Mtb is disseminated to many other organs and tissues. Dissemination occurs early during the disease, and bacteria can be found first in the lymph nodes adjacent to the lungs and then later in the extrapulmonary organs, including the spleen. The early global gene expression response of human tissue macrophages and intracellular clinical isolates of Mtb has been poorly studied. Using dual RNA-seq, we have explored the mRNA profiles of two closely related clinical strains of the Latin American and Mediterranean (LAM) family of Mtb in infected human splenic macrophages (hSMs). This work shows that these pathogens mediate a distinct host response despite their genetic similarity. Using a genome-scale host–pathogen metabolic reconstruction to analyze the data further, we highlight that the infecting Mtb strain also determines the metabolic response of both the host and pathogen. Thus, macrophage ontogeny and the genetic-derived program of Mtb direct the host–pathogen interaction.

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Section: Introductionmentioning

confidence: 99%

Dual RNA Sequencing of Mycobacterium tuberculosis-Infected Human Splenic Macrophages Reveals a Strain-Dependent Host–Pathogen Response to Infection

López-Agudelo

Baena

Barrera

et al. 2022

IJMS

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“… 13 An ongoing immune response against the cavitary lesion could result in further increase in the percentage of blood monocytes. 14 15 16 Moreover, lymphopenia could result from the accumulation of lymphocytes at the infection site, leading to their decreased number in the peripheral blood. 17 These theoretical changes in neutrophils, lymphocytes, and monocytes can reasonably explain why NLR and MLR were increased in accordance with the radiologic severity in MAC-PD.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio According to the Radiologic Severity of Mycobacterium avium Complex Pulmonary Disease

et al. 2022

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Background To date, no study has investigated whether the neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) have a clinical value in Mycobacterium avium complex (MAC)-pulmonary disease (PD). Methods We aimed to assess whether the baseline NLR and MLR were different according to the severity of MAC-PD based on the radiologic classification by retrospectively analyzing 549 patients treated in a tertiary referral center in South Korea. Results Both NLR and MLR were significantly higher as 3.33 and 0.43 respectively in the fibrocavitary type, followed by 2.34 and 0.27 in the cavitary nodular bronchiectatic type and significantly lower as 1.88 and 0.23 in the non-cavitary nodular bronchiectatic type. Conclusion The baseline NLR and MLR showed a distinct difference in accordance with the radiologic severity of MAC-PD.

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“…34 All these immune cells have been shown to play a crucial role in controlling TB infection. [35][36][37] Thus, TYROBP is indirectly involved in maintaining the infection of TB via controlling the activation of various immune cells. Furthermore, several studies confirm the role of the TYROBP gene product in the pathophysiology of TB through network analysis.…”

Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Biomarker with Potential of High Diagnostic Accuracy in Pulmonary Tuberculosis: An in silico Study

Sheikh

Bhat

Mir

et al. 2022

IJPI

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Background: Due to the fact that pulmonary tuberculosis (PTB) is a highly infectious disease characterized by high herd susceptibility and hard to be treated. Cytokines have a crucial role in eliciting protective and pathologic consequences in infectious diseases, including tuberculosis. This study aimed to investigate the gene expression dataset of tuberculosis patients to identify the novel cytokine biomarkers in pulmonary tuberculosis. Materials and Methods: The expression dataset (GSE19435) having comparative study of drug treatment at 0-month (control), 2-months and 12 months was retrieved from National Center for Biotechnology Information (NCBI) geo datasets for bioinformatic analysis. Differential gene expression (DEGs) analysis of immune-related genes with treatment progression was performed which was further followed by Protein-Protein Interaction (PPI) network construction. Further, functional enrichment and KEGG pathway enrichment analysis were also performed. Finally, Receiver-operating characteristic curves (ROC) analysis was performed for selected biomarkers. Results: A total of 210 differentially expressed genes (DEGs) were identified, out of which 59 were upregulated, while 151 were downregulated. Gene ontology results revealed that the deregulated genes were enriched in immune response-regulation, cytokine pathways, and response to the bacterium. Also, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that deregulated genes are involved in the fork head box transcription factors (FOXO) signaling pathway, oxidative phosphorylation, and osteoclast differentiation pathways. Based on the combined score and degree of connectedness, novel genes like amyloid-beta precursor protein (APP), Transmembrane Immune Signaling Adaptor (TYROBP), Annexin A2 (ANXA2), Proteasome 20S Subunit Beta 2 (PSMB2), CD58 Molecule (CD58) (upregulated genes), and Thyroid Hormone Receptor Interactor 12 (TRIP12), RNA Polymerase III Subunit A (POLR3A), Nuclear Factor of Activated T Cells 5 (NFAT5), DEAD-Box Helicase 17 (DDX17), DNA Topoisomerase III (TOP3A) (downregulated genes) were identified as hub genes of which TRIP12 and POLR3A are cytokines (type1) biomarkers. Further analysis through ROC divulged TRIP12 as a potential diagnostic biomarker. Conclusion: Overall findings revealed that TRIP12 is a novel cytokine biomarker in Mycobacterium tuberculosis-infected patients with the highest diagnostic accuracy.

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Infection of Monocytes From Tuberculosis Patients With Two Virulent Clinical Isolates of Mycobacterium tuberculosis Induces Alterations in Myeloid Effector Functions

Cited by 11 publications

References 95 publications

Dual RNA Sequencing of Mycobacterium tuberculosis-Infected Human Splenic Macrophages Reveals a Strain-Dependent Host–Pathogen Response to Infection

Dual RNA Sequencing of Mycobacterium tuberculosis-Infected Human Splenic Macrophages Reveals a Strain-Dependent Host–Pathogen Response to Infection

Neutrophil-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio According to the Radiologic Severity of Mycobacterium avium Complex Pulmonary Disease

A Novel Prognostic Biomarker with Potential of High Diagnostic Accuracy in Pulmonary Tuberculosis: An in silico Study

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