Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status

Yu, Elaine A.; John, Serene H.; Tablante, Elizabeth Centeno; King, Christine A.; Kenneth, John; Russell, David G.; Mehta, Saurabh

doi:10.1371/journal.pone.0185640

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…For instance, a study in Norway showed that LTBI was associated with increased serum levels of interleukin 1β, 6, and 22 and tumor necrosis factor α 22 . LTBI status was also associated with higher levels of monocyte/macrophage activation markers and chemo‐tactic mediators, such as CD14, 23 CXCL2, CXCL3, and IL8 24 . Another study reported a subtle increase in circulating interferon γ concentrations in persons with LTBI in the United States, compared with controls without LTBI 25 .…”

Section: Discussionmentioning

confidence: 99%

Risk factors and prognosis for latent tuberculosis infection in dialysis patients: A retrospective cohort study at a single tertiary care center

Xia

Fan

Zhang

et al. 2023

Seminars in Dialysis

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IntroductionRecent studies report that latent tuberculosis infection (LTBI) may lead to an increased risk of cardiovascular disease (CVD) that led us to hypothesize that LTBI may play an important role in major adverse cardiovascular events (MACE) in dialysis patients.MethodsA single‐center retrospective cohort study was conducted. A total of 270 patients undergoing hemodialysis or peritoneal dialysis more than 3 months were included. The interferon enzyme‐linked immunospot (IFN‐γ ELISPOT) assay was used for the diagnosis of LTBI. Primary endpoints were MACE, including all‐cause death and acute coronary syndrome (ACS). The association between LTBI and MACE was examined using multivariate Cox proportional hazards regression after adjusting for covariates and Kaplan–Meier survival analysis.ResultsIn our study, the patients were classified into LTBI (n = 47) or non‐LTBI (n = 223) groups. Independent risk factors for LTBI in dialysis population were prior tuberculosis (TB) history (odds ratio [OR] 4.817 [1.064–22.306]), tobacco use (OR 2.903 [1.155–7.299]), and older age (OR 1.027 [1.002–1.053]). After a median follow‐up of 39 months, the incidence of active TB was 6.4% versus 0% in dialysis patients with and without LTBI, respectively (p = 0.005). Multivariate Cox analysis showed that LTBI was significantly associated with MACE (hazard ratio [HR] 2.540 [1.490–4.350]) after adjustment for potential confounders.ConclusionsPrior TB history, tobacco use, and the elderly can be used to select cost‐effective LTBI screening target groups in dialysis patients. LTBI is not only closely related to active TB but also an independent risk factor for higher incidence of MACE in dialysis population.

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Section: Discussionmentioning

confidence: 99%

Risk factors and prognosis for latent tuberculosis infection in dialysis patients: A retrospective cohort study at a single tertiary care center

Xia

Fan

Zhang

et al. 2023

Seminars in Dialysis

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“…GBP2 is one of the prominent hubs in a highly active common core in TB [36]. Blocking CXCL2 could reduce the M. tuberculosis-induced IL-1β production [37,38]. Exposure of murine peritoneal macrophages to M. tuberculosis increases SLPI secretion and accelerates both the phagocytosis and killing of the pathogen [39][40][41], possibly by interacting with S100A8/A9 proteins to decrease lung tissue damage without affecting protective immunity against TB [42].…”

Section: Discussionmentioning

confidence: 99%

Effects of Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes

et al. 2020

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Background: Tuberculosis is a leading cause of death worldwide. BCG is an effective vaccine, but not widely used in many parts of the world due to a variety of issues. Mycobacterium vaccae (M. vaccae) is another vaccine used in human subjects to prevent tuberculosis. In the current study, we investigated the potential mechanisms of M. vaccae vaccination by determining differentially expressed genes in mice infected with M. tuberculosis before and after M. vaccae vaccination. Methods: Three days after exposure to M. tuberculosis H37Rv strain (5 × 10 5 CFU), adult BALB/c mice randomly received either M. vaccae vaccine (22.5 μg) or vehicle via intramuscular injection (n = 8). Booster immunization was conducted 14 and 28 days after the primary immunization. Differentially expressed genes were identified by microarray followed by standard bioinformatics analysis. Results: M. vaccae vaccination provided protection against M. tuberculosis infection (most prominent in the lungs). We identified 2326 upregulated and 2221 downregulated genes in vaccinated mice. These changes could be mapped to a total of 123 signaling pathways (68 upregulated and 55 downregulated). Further analysis pinpointed to the MyD88dependent TLR signaling pathway and PI3K-Akt signaling pathway as most likely to be functional. Conclusions: M. vaccae vaccine provided good protection in mice against M. tuberculosis infection, via a highly complex set of molecular changes. Our findings may provide clue to guide development of more effective vaccine against tuberculosis.

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“…For example, CCR2 and its ligands MCP-1, MCP-2, and MCP-3, which recruit monocytes to the lung, are significantly increased upon M. tuberculosis infection (19, 29, 30). Similarly, mice lacking CD38, a sister molecule of CD157 with 33% homology in amino acid sequence, are highly susceptible to Mycobacterium avium without impaired immune cell recruitment to the lung (8).…”

Section: Discussionmentioning

confidence: 99%

CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production

Yang

Liao

Wang

et al. 2019

mBio

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Recruitment of monocytes to the infection site is critical for host resistance against Mycobacterium tuberculosis. CD157 has a crucial role in neutrophil and monocyte transendothelial migration and adhesion, but its role in tuberculosis (TB) is unclear. Here, we show that both mRNA and protein levels of Cd157 are significantly increased during M. tuberculosis infection. Deficiency of Cd157 impaired host response to M. tuberculosis infection by increasing bacterial burden and inflammation in the lung in the murine TB model. In vitro experiments show that the bactericidal ability was compromised in Cd157 knockout (KO) macrophages, which was due to impaired M. tuberculosis-induced reactive oxygen species (ROS) production. We further reveal that CD157 interacts with TLR2 and PKCzeta and facilitates M. tuberculosis-induced ROS production in Cd157 KO macrophages, which resulted in enhanced M. tuberculosis killing. For the clinic aspect, we observe that the expression of CD157 decreases after effective anti-TB chemotherapy. CD157 is specifically increased in pleural fluid in tuberculous pleurisy patients compared to pneumonia and lung cancer patients. Interestingly, the levels of soluble CD157 (sCD157) correlate with human peripheral monocyte-derived macrophage bactericidal activity. Exogenous application of sCD157 could compensate for macrophage bactericidal ability and restore ROS production. In conclusion, we have identified a novel protective immune function of CD157 during M. tuberculosis infection via TLR2-dependent ROS production. Application of sCD157 might be an effective strategy for host-directed therapy against TB in those with insufficient CD157 production. IMPORTANCE Tuberculosis, a chronic bacterial disease caused by Mycobacterium tuberculosis, remains a major global health problem. CD157, a dual-function receptor and β-NAD+-metabolizing ectoenzyme, promotes cell polarization, regulates chemotaxis induced through the high-affinity fMLP receptor, and controls transendothelial migration. The role of CD157 in TB pathogenesis remains unknown. In this study, we find that both mRNA and protein levels of CD157 are significantly increased in TB. Deficiency of CD157 impaired host defense against M. tuberculosis infection both in vivo and in vitro, which is mediated by an interaction among CD157, TLR2, and PKCzeta. This interaction facilitates M. tuberculosis-induced macrophagic ROS production, which enhances macrophage bactericidal activity. Interestingly, the sCD157 level in plasma is reversibly associated with MDM M. tuberculosis killing activity. By uncovering the role of CD157 in pathogenesis of TB for the first time, our work demonstrated that application of soluble CD157 might be an effective strategy for host-directed therapy against TB.

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Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status

Cited by 6 publications

References 37 publications

Risk factors and prognosis for latent tuberculosis infection in dialysis patients: A retrospective cohort study at a single tertiary care center

Risk factors and prognosis for latent tuberculosis infection in dialysis patients: A retrospective cohort study at a single tertiary care center

Effects of Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes

CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production

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