Single-cell TCR sequencing analysis of the course of Mycobacterium avium complex pulmonary disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE226442 | GEO | 2024/03/01
REPOSITORIES: GEO
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Project description:We performed scRNA-seq to investigate overall immune cell populations and distribution of MAC-PD patients, according to their clinical outcome.
2024-03-01 | GSE226099 | GEO
Project description:The incidence of Mycobacterium avium complex (MAC)-induced pulmonary disease (PD) has been increasing in South Korea, posing considerable challenges in treatment. Treatment guidelines recommend initiating therapy after serial computed tomography (CT) monitoring. While drug treatment often improves outcomes in patients with the nodular bronchiectatic (NB) form, those with the fibrocavitary (FC) form may continue to experience persistence despite treatment. Our objective was to classify type-specific and common genes based on radiological phenotypes (NB and FC) using RNA sequencing to analyze the cellular landscape of 11 NB sections, 10 FC sections, and 21 unaffected sections from 21 MAC-PD cases. Predictive in silico analysis indicated a significant role for genes related to B cell proliferation and regulation in both forms. Additionally, NB patients exhibited predominantly regulated antimicrobial immune responses, whereas FC patients showed enrichment in genes related to extracellular matrix structure. These target genes identified through genetic analysis could potentially serve as predictive biomarkers for type-specific biological processes and cellular pathways, necessitating further validation studies.
2024-07-01 | GSE270278 | GEO
Project description:Mycobacterium avium complex (MAC) is a non-tuberculosis mycobacteria widely distributed throughout environment. Even though the MAC infection is currently increasing in old women and patients with affected immune system, comprehensive analysis of MAC-infected host cell transcriptome, in particular that of long non-coding RNAs (lncRNAs), has scarcely been reported. Using in vitro cultured primary mouse bone marrow-derived macrophages (BMDMs) and CAGE technology, we analyzed the transcriptional and kinetic landscape of macrophage genes, with focusing on lncRNAs, during MAC infection. MAC-infected macrophages induced immune/inflammatory response genes and other genes as similar as M1 activation, consistent with previous reports, although Nos2 and Arg1 revealed distinct expression profiles from M1 activation. We identified 31 up-regulated and 30 down-regulated lncRNA promoters corresponding to 18 and 27 lncRNAs, respectively. The up-regulated lncRNAs were clustered into two groups, early and late up-regulated groups, which were predicted to associate with the immune activation and the immune response to infection, respectively. Further, the Ingenuity IPA analysis predicted canonical pathways and upstream transcription regulators associated with differentially expressed lncRNAs. Several differentially expressed lncRNAs that have been reported elsewhere revealed various expressional change by M1 or M2 pre-activation and the following MAC infection. Finally, we showed that expressional change of lncRNAs in MAC-infected BMDMs is predominantly mediated by Tlr2, but there may be other weakly sensing mechanism for MAC infection. Taken together, we identified differentially expressed lncRNAs in MAC-infected BMDMs, which revealed diverse features implying their distinct role in MAC infection and macrophage polarization.
2024-01-01 | GSE249460 | GEO
Project description:Rationale: T cell activation is a key antimicrobial component against mycobacterial disease. Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway could affect the antimicrobial immune responses by suppressing T cell activity. Several recent studies demonstrated that blocking of PD-1/PD-L1 pathway exacerbated Mycobacterium tuberculosis infection. However, the influence of blocking this pathway in pulmonary Mycobacterium avium-intracellulare complex (MAC) infection was not fully understood. Objective: We aimed to determine the influence of genetic depletion of PD-1/PD-L1 pathway on the disease activity of MAC infection. Methods: Wild-type, PD-1-deficient mice and PD-L1-deficient mice were intranasally infected with Mycobacterium avium bacteria. Measurements and Main Results: The depletion of PD-1 or PD-L1 did not affect mortality and bacterial burden in mice infected with MAC. However, remarkable infiltration of CD8 T lymphocytes was observed in the lungs of PD-1 and PD-L1 deficient mice compared to wild-type mice. Comprehensive transcriptome analysis showed that levels of gene expressions related to Th1 immunity did not differ according to the genotypes. However, genes related to the activity of CD8 T cells and related chemokine activity were up-regulated in the infected lungs of PD-1 and PD-L1 deficient mice. Conclusions: Depletion of PD-1/PD-L1 pathway did not affect the activation of Th1 immunity in response to MAC infection, which may explain why MAC infection was controlled in these mice. In addition, CD8-positive T cell pulmonary inflammation in knockout mice might have some clinical implication in the treatment of cancer patients with immune checkpoint inhibitors when the patients are infected with MAC.
2021-09-15 | GSE169202 | GEO
Project description:BackgroundThere is no proven management for mild cases of Mycobacterium avium complex (MAC) pulmonary disease, who do not immediately receive treatment and are managed with observation alone, because its long term-natural course, factors predictive of deterioration, and the effect of treating the disease remain unclear. Thus, we sought to investigate the natural course of mild cases of MAC pulmonary disease.MethodsWe conducted a multicenter retrospective study. Sixty-five patients with mild MAC pulmonary disease in whom treatment was withheld for at least 6 months after diagnosis were retrospectively recruited after a review of 747 medical records. Longitudinal changes in clinical features were evaluated by using a mixed effects model.ResultsMean follow-up was 6.9 ± 5.7 years. During the follow-up period, 15 patients (23%) required treatment and 50 (77%) were managed with observation alone. At diagnosis, 65 patients had nodular bronchiectatic disease without fibrocavitary lesions. Among clinical features, mean body mass index (BMI), forced expiratory volume in 1 second as percent of forced vital capacity (%FEV1), nodular lung lesions, and bronchiectasis worsened significantly in the observation group during follow-up. In the treatment group, BMI, and %FEV1 were stable, but bronchiectasis significantly worsened. At diagnosis, the polyclonal MAC infection rate in the treatment group was higher than that in the observation group. Other microbiological factors, such as insertion sequences, did not differ significantly between the groups.ConclusionsMild MAC pulmonary disease progresses slowly but substantially without treatment. Treatment prevents the deterioration of the disease but not the progression of bronchiectasis. Polyclonal MAC infection is a predictor of disease progression.
| S-EPMC6483267 | biostudies-literature
Project description:WGS of MAC strains from infected BALB/c mice
| PRJDB12771 | ENA
Project description:The combination of rifamycin (RFP), ethambutol (EB), and macrolides is currently the standard regimen for treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). However, poor adherence to the standardized regimens recommended by current guidelines have been reported. We undertook a single-centred retrospective cohort study to evaluate the long-term outcomes in 295 patients with MAC-PD following first line treatment with standard (RFP, EB, clarithromycin [CAM]) or alternative (EB and CAM with or without fluoroquinolones (FQs) or RFP, CAM, and FQs) regimens. In this cohort, 80.7% were treated with standard regimens and 19.3% were treated with alternative regimens. After heterogeneity was statistically corrected using propensity scores, outcomes were superior in patients treated with standard regimens. Furthermore, alternative regimens were significantly and independently associated with sputum non-conversion, treatment failure and emergence of CAM resistance. Multivariate cox regression analysis revealed that older age, male, old tuberculosis, diabetes mellitus, higher C-reactive protein, and cavity were positively associated with mortality, while higher body mass index and M. avium infection were negatively associated with mortality. These data suggest that, although different combination regimens are not associated with mortality, first line administration of a standard RFP?+?EB?+?macrolide regimen offers the best chance of preventing disease progression in MAC-PD patients.
| S-EPMC7807086 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-03-01 | GSE226473 | GEO
Project description:BACKGROUND:Multidrug therapy is essential for preventing respiratory failure in patients with highly progressive Mycobacterium avium complex pulmonary disease (MAC-PD). However, the prognosis and long-term outcome following combination therapy is poorly understood. METHODS:We retrospectively evaluated the clinical characteristics and long-term outcomes in patients with chemo-naïve progressive MAC-PD, hospitalized for first-line multidrug therapy. RESULTS:Among 125 patients, 86 (68.8%) received standardized treatment (rifampicin, ethambutol, clarithromycin), 25 (20.0%) received a fluoroquinolone (FQ)-containing regimen, and 53 (42.4%) received aminoglycoside injection. The sputum conversion rate was 80.0%, and was independently associated with standardized treatment. The incidence of refractory disease (45.6%) was independently and negatively associated with standardized regimen and aminoglycoside use. Choice of an FQ-containing regimen was not associated with positive outcome. Clarithromycin resistance occurred in 16.8% and was independently associated with refractory disease. MAC-PD-associated death occurred in 3.3% of patients with non-cavitary nodular bronchiectasis (NB) and 21.3% with cavitary MAC-PD over a median follow-up period of 56.4 months. The rates of MAC-PD-associated death were comparable between cavitary-NB and fibrocavitary disease. Concurrent chronic pulmonary aspergillosis (CPA) occurred in 13 (17.3%) patients with cavitary MAC-PD, and age, diabetes mellitus, and CPA were independent risk factors for mortality. CONCLUSIONS:Standardized intensive multidrug treatment reduces disease progression and persistence in progressive MAC-PD. Cavitary NB may differ from, rather than being just an advanced stage of, non-cavitary NB. The high incidence and significant mortality of CPA in cavitary MAC-PD highlight the need for early diagnosis and treatment.
| S-EPMC7291046 | biostudies-literature
Project description:The Mycobacterium abscessus complex (MABC) comprises rapidly growing mycobacteria and has received increasing attention recently, with an increasing number of associated infections reported worldwide. However, the clinical features of MABC pulmonary disease (MABC-PD), especially in terms of the chest computed tomography (CT) findings, are not fully understood. Thus, this retrospective, cross-sectional study aimed to evaluate the clinical background and chest high-resolution CT (HRCT) findings of MABC-PD in comparison with those of Mycobacterium avium complex PD (MAC-PD). Accordingly, 36 patients with MABC-PD and 65 patients with MAC-PD (defined according to the American Thoracic Society criteria), who were newly diagnosed at four major hospitals in Okinawa (Japan) between January 2012 and December 2017, were analyzed. With respect to their clinical background, only cardiovascular diseases were significantly more common in patients with MABC-PD than in those with MAC-PD (38.9% vs. 18.5%, p = 0.0245). HRCT revealed a significantly higher incidence of low attenuation in patients with MABC-PD than in those with MAC-PD (63.9% vs. 10.8%, p<0.0001). On analyzing only never-smokers (20 and 47 patients with MABC-PD and MAC-PD, respectively), this significant difference remained (65.0% vs. 8.5%, p<0.0001), suggesting MABC infection itself caused low attenuation. In terms of the distribution of abnormal shadows, the involvement of the right lower, left upper, and left lower lobes was more common in patients with MABC-PD than in those with MAC-PD. Furthermore, the mean number of involved lung lobes was significantly higher in patients with MABC-PD than in those with MAC-PD (5.6 vs. 4.7, p<0.001). Although further studies are needed, we assume that the aforementioned radiological features of MABC-PD are due to the high virulence of MABC.
| S-EPMC9302740 | biostudies-literature