Neutrophil CD64, TLR2 and TLR4 expression increases but phagocytic potential decreases during tuberculosis

Hilda, J. Nancy; Das, Sulochana D.

doi:10.1016/j.tube.2018.06.010

Cited by 20 publications

(11 citation statements)

References 33 publications

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“…Toll-like receptors play key roles in innate and adaptive immunity against Mtb, and are involved in the recognition of conserved microbial structures, leading to activation of an inflammatory response. Previous study showed that TLR3 and TLR5 were upregulated at 24, 48 and 72 h post-infection in A549 pulmonary epithelial cells treated with Mtb [ 21 ], and the expression of neutrophil TLR2 is also increased in PTB patients [ 22 ]. Whole blood from patients had increased mRNA levels of TLR1 and TLR2 [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Gene network in pulmonary tuberculosis based on bioinformatic analysis

et al. 2020

BMC Infect Dis

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Background: Pulmonary tuberculosis (PTB) is one of the serious infectious diseases worldwide; however, the gene network involved in the host response remain largely unclear. Methods: This study integrated two cohorts profile datasets GSE34608 and GSE83456 to elucidate the potential gene network and signaling pathways in PTB. Differentially expressed genes (DEGs) were obtained for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using Metascape database. Protein-Protein Interaction (PPI) network of DEGs was constructed by the online database the Search Tool for the Retrieval of Interacting Genes (STRING). Modules were identified by the plug-in APP Molecular Complex Detection (MCODE) in Cytoscape. GO and KEGG pathway of Module 1 were further analyzed by STRING. Hub genes were selected for further expression validation in dataset GSE19439. The gene expression level was also investigated in the dataset GSE31348 to display the change pattern during the PTB treatment. Results: Totally, 180 shared DEGs were identified from two datasets. Gene function and KEGG pathway enrichment revealed that DEGs mainly enriched in defense response to other organism, response to bacterium, myeloid leukocyte activation, cytokine production, etc. Seven modules were clustered based on PPI network. Module 1 contained 35 genes related to cytokine associated functions, among which 14 genes, including chemokine receptors, interferon-induced proteins and Toll-like receptors, were identified as hub genes. Expression levels of the hub genes were validated with a third dataset GSE19439. The signature of this core gene network showed significant response to Mycobacterium tuberculosis (Mtb) infection, and correlated with the gene network pattern during anti-PTB therapy. Conclusions: Our study unveils the coordination of causal genes during PTB infection, and provides a promising gene panel for PTB diagnosis. As major regulators of the host immune response to Mtb infection, the 14 hub genes are also potential molecular targets for developing PTB drugs.

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Section: Discussionmentioning

confidence: 99%

Gene network in pulmonary tuberculosis based on bioinformatic analysis

et al. 2020

BMC Infect Dis

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“…The role of neutrophils in TB is complex and is likely to vary at different stages of infection and disease (29). Despite their numerical predominance, the functional significance of circulating neutrophils with presumptive high levels of expression of FCGR1 is not known (30). If they reflect the status of neutrophils within TB lesions, then the abundance and high affinity of this IgG receptor may have a key involvement in modulation of innate and acquired immunity in addition to pathology of PTB (31).…”

Section: Discussionmentioning

confidence: 99%

Probe Signal Values in mRNA Arrays Imply an Excessive Involvement of Neutrophil FCGR1 in Tuberculosis

Chen

et al. 2020

Front. Med.

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The perturbed genes from transcriptomes are often presented in terms of relative expressions against control samples. However, the probe signal values (PSVs) of genes, implying protein abundances, are often ignored. Here, we explored the PSVs in tuberculosis (TB)-relevant signature genes. The signatures from Mycobacterium tuberculosis-infected THP-1 cells were defined as induced (TMtb-i, with a derived TMtb-iNet) and repressed (TMtb-r). The signature from human blood was defined as a pulmonary TB (PTB)-specific signature (PTBsig). The analysis showed that before infection, TMtb-i and TMtb-iNet had lower PSVs and TMtb-r genes had average PSVs. In the blood of healthy donors, PTBsig (divided into up-regulated PTBsigUp and down-regulated PTBsigDn) displayed average PSVs. This was partly due to masking by the cellular heterogeneity of blood; diverse PSVs were seen in constituent cell populations (CD4/8+ T, monocytes and neutrophils). Specifically, the PSVs of PTBsigUp in the neutrophils of healthy donors were higher (implying higher protein abundances), and much higher in the neutrophils of PTB (implying excessive protein abundances). Based on the PSV patterns of PTBsigUp in four cell populations, we identified three representative highly homologous genes (FCGR1A, FCGR1B, and the pseudogene FCGR1CP, which were often poorly distinguished), of which the summed PSVs were the highest in the neutrophils of PTB patients and healthy donors. The three genes were all up-regulated and responsive to chemotherapy in the blood of PTB, as validated in an RNA-seq-based analysis. This PSV-based study confirms the excessive involvement of neutrophil FCGR1 in PTB.

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“…Surface expression of the Ig receptor FcγR1 (CD64) was found to be increased on peripheral blood neutrophils from patients with tuberculosis pleuritis compared to healthy controls, and neutrophils obtained from pleural fluid showed further enhanced FcγR1 expression and increased expression of the pattern recognition receptor TLR2 ( 132 ). An increase in expression of FcγR1, TLR2 and TLR4 was also observed in neutrophils from the peripheral blood of patients with active pulmonary tuberculosis prior to treatment ( 133 ). Despite the evidence for increased receptor expression, studies examining the phagocytic activity of neutrophils from patients with active pulmonary tuberculosis generally show their capacity for phagocytosis is decreased.…”

Section: Neutrophil Phagocytosis Of Mycobacteriamentioning

confidence: 97%

“…Hilda et al. measured significantly reduced phagocytic activity in blood neutrophils from patients prior to treatment ( 133 ), and Shalekoff et al also found peripheral blood neutrophil function impaired in patients with active pulmonary tuberculosis ( 134 ). Patient neutrophils showed a reduced capacity for phagocytosis compared to healthy controls and this was observed both soon after the start of treatment and when treatment had been undertaken for almost 30 weeks ( 134 ).…”

Section: Neutrophil Phagocytosis Of Mycobacteriamentioning

confidence: 99%

Antimicrobial Activity of Neutrophils Against Mycobacteria

et al. 2021

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The mycobacterium genus contains a broad range of species, including the human pathogens M. tuberculosis and M. leprae. These bacteria are best known for their residence inside host cells. Neutrophils are frequently observed at sites of mycobacterial infection, but their role in clearance is not well understood. In this review, we discuss how neutrophils attempt to control mycobacterial infections, either through the ingestion of bacteria into intracellular phagosomes, or the release of neutrophil extracellular traps (NETs). Despite their powerful antimicrobial activity, including the production of reactive oxidants such as hypochlorous acid, neutrophils appear ineffective in killing pathogenic mycobacteria. We explore mycobacterial resistance mechanisms, and how thwarting neutrophil action exacerbates disease pathology. A better understanding of how mycobacteria protect themselves from neutrophils will aid the development of novel strategies that facilitate bacterial clearance and limit host tissue damage.

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Neutrophil CD64, TLR2 and TLR4 expression increases but phagocytic potential decreases during tuberculosis

Cited by 20 publications

References 33 publications

Gene network in pulmonary tuberculosis based on bioinformatic analysis

Gene network in pulmonary tuberculosis based on bioinformatic analysis

Probe Signal Values in mRNA Arrays Imply an Excessive Involvement of Neutrophil FCGR1 in Tuberculosis

Antimicrobial Activity of Neutrophils Against Mycobacteria

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