CD4 T cell help prevents CD8 T cell exhaustion and promotes control of<i>Mycobacterium tuberculosis</i>infection

Lu, Yu-Jung; Barreira-Silva, Palmira; Boyce, Shayla; Powers, Jennifer; Cavallo, Kelly; Behar, Samuel M.

doi:10.1101/2021.02.23.432461

Cited by 4 publications

(4 citation statements)

References 66 publications

(29 reference statements)

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“…Host immune response is the major mechanism against MTB infection (Mayer-Barber and Barber, 2015;Lu et al, 2021;Rijnink et al, 2021). Immune cell infiltration assessment revealed enhanced inflammatory and myeloid cell levels (DCs, monocytes, and neutrophils) in ATB patients than in LTBI patients, whereas adaptive immunity cells (active CD8 T and B cells) indicated reduced expression.…”

Section: Discussionmentioning

confidence: 99%

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Identification of apoptosis-related gene signatures as potential biomarkers for differentiating active from latent tuberculosis via bioinformatics analysis

Dai,

Zhou,

et al. 2024

Front. Cell. Infect. Microbiol.

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BackgroundApoptosis is associated with the pathogenesis of Mycobacterium tuberculosis infection. This study aims to identify apoptosis-related genes as biomarkers for differentiating active tuberculosis (ATB) from latent tuberculosis infection (LTBI).MethodsThe tuberculosis (TB) datasets (GSE19491, GSE62525, and GSE28623) were downloaded from the Gene Expression Omnibus (GEO) database. The diagnostic biomarkers differentiating ATB from LTBI were identified by combining the data of protein-protein interaction network, differentially expressed gene, Weighted Gene Co-Expression Network Analysis (WGCNA), and receiver operating characteristic (ROC) analyses. Machine learning algorithms were employed to validate the diagnostic ability of the biomarkers. Enrichment analysis for biomarkers was established, and potential drugs were predicted. The association between biomarkers and N6-methyladenosine (m6A) or 5-methylated cytosine (m5C) regulators was evaluated.ResultsSix biomarkers including CASP1, TNFSF10, CASP4, CASP5, IFI16, and ATF3 were obtained for differentiating ATB from LTBI. They showed strong diagnostic performances, with area under ROC (AUC) values > 0.7. Enrichment analysis demonstrated that the biomarkers were involved in immune and inflammation responses. Furthermore, 24 drugs, including progesterone and emricasan, were predicted. The correlation analysis revealed that biomarkers were positively correlated with most m6A or m5C regulators.ConclusionThe six ARGs can serve as effective biomarkers differentiating ATB from LTBI and provide insight into the pathogenesis of Mycobacterium tuberculosis infection.

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Section: Discussionmentioning

confidence: 99%

“…Construction of biomarker genes-drug network (H). Dai et al 10.3389/fcimb.2024.1285493 Tcell responses (Lu et al, 2021). These T cells and antibodies granuloma formation, thereby affecting the progression of MTB infection.…”

Section: Discussionmentioning

confidence: 99%

Identification of apoptosis-related gene signatures as potential biomarkers for differentiating active from latent tuberculosis via bioinformatics analysis

Dai,

Zhou,

et al. 2024

Front. Cell. Infect. Microbiol.

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“…The early interplay between host innate immunity and Mtb determines the establishment and progression of TB infection (Liu et al, 2017a;Lu et al, 2021). About 50% of people who are close contacts of TB patients test negative in the tuberculin skin test, which detects the involvement of adaptive immunity to TB (Lerner et al, 2015;Tomlinson et al, 2011).…”

Section: The Host-mtb Interactionsmentioning

confidence: 99%

Gaucher disease protects against tuberculosis

Fan

Hale

Lelieveld

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Biallelic mutations in the glucocerebrosidase ( GBA1 ) gene cause Gaucher disease, characterized by lysosomal accumulation of glucosylceramide and glucosylsphingosine in macrophages. Gaucher and other lysosomal diseases occur with high frequency in Ashkenazi Jews. It has been proposed that the underlying mutations confer a selective advantage, in particular conferring protection against tuberculosis. Here, using a zebrafish Gaucher disease model, we find that the mutation GBA1 N370S, predominant among Ashkenazi Jews, increases resistance to tuberculosis through the microbicidal activity of glucosylsphingosine in macrophage lysosomes. Consistent with lysosomal accumulation occurring only in homozygotes, heterozygotes remain susceptible to tuberculosis. Thus, our findings reveal a mechanistic basis for protection against tuberculosis by GBA1 N370S and provide biological plausibility for its selection if the relatively mild deleterious effects in homozygotes were offset by significant protection against tuberculosis, a rampant killer of the young in Europe through the Middle Ages into the 19th century.

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“…Moreover, immune cells such as macrophages and dendritic cells can present antigens to T and B cells and augment adaptive immune responses. After infection, CD4+ T cells can not only further strengthen the innate immunity but also promote the function and survival of CD8+ T cells (Lu et al, 2021), whilst CD8+ T cells can directly kill M. tuberculosis by their cytolytic function (Lin and Flynn, 2015). Antibody opsonization was also shown to promote the phagocytosis of macrophages (Chandra et al, 2022).…”

Section: Microbiome-immune Crosstalk During M Tuberculosis Infectionmentioning

confidence: 99%

The gut microbiome: A line of defense against tuberculosis development

Shen

Wang

et al. 2023

Front. Cell. Infect. Microbiol.

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The tuberculosis (TB) burden remains a significant global public health concern, especially in less developed countries. While pulmonary tuberculosis (PTB) is the most common form of the disease, extrapulmonary tuberculosis, particularly intestinal TB (ITB), which is mostly secondary to PTB, is also a significant issue. With the development of sequencing technologies, recent studies have investigated the potential role of the gut microbiome in TB development. In this review, we summarized studies investigating the gut microbiome in both PTB and ITB patients (secondary to PTB) compared with healthy controls. Both PTB and ITB patients show reduced gut microbiome diversity characterized by reduced Firmicutes and elevated opportunistic pathogens colonization; Bacteroides and Prevotella were reported with opposite alteration in PTB and ITB patients. The alteration reported in TB patients may lead to a disequilibrium in metabolites such as short-chain fatty acid (SCFA) production, which may recast the lung microbiome and immunity via the “gut-lung axis”. These findings may also shed light on the colonization of Mycobacterium tuberculosis in the gastrointestinal tract and the development of ITB in PTB patients. The findings highlight the crucial role of the gut microbiome in TB, particularly in ITB development, and suggest that probiotics and postbiotics might be useful supplements in shaping a balanced gut microbiome during TB treatment.

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CD4 T cell help prevents CD8 T cell exhaustion and promotes control ofMycobacterium tuberculosisinfection

Cited by 4 publications

References 66 publications

Identification of apoptosis-related gene signatures as potential biomarkers for differentiating active from latent tuberculosis via bioinformatics analysis

Identification of apoptosis-related gene signatures as potential biomarkers for differentiating active from latent tuberculosis via bioinformatics analysis

Gaucher disease protects against tuberculosis

The gut microbiome: A line of defense against tuberculosis development

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