Possible Mechanisms of Lymphopenia in Severe Tuberculosis

Li, Fei; Chen, Dandan; Zeng, Qingqing; Du, Yunjie

doi:10.3390/microorganisms11112640

Cited by 3 publications

(3 citation statements)

References 121 publications

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“…3 D). The increased activity observed in C3 suggests an augmented demand for blood cells throughout the disease process, driven by heightened immune responses and inflammation, which potentially leads to escalated blood cell consumption and demand 30 . Additionally, the closely intertwined relationship between reactive oxygen species (ROS) and oxidative stress pathways with macrophages in tuberculosis underscores the pivotal role of these pathways in combating PTB infection (Fig.…”

Section: Resultsmentioning

confidence: 99%

Multi-cohort analysis reveals immune subtypes and predictive biomarkers in tuberculosis

Li,

Wang,

Chen

et al. 2024

Sci Rep

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Tuberculosis (TB) remains a significant global health threat, necessitating effective strategies for diagnosis, prognosis, and treatment. This study employs a multi-cohort analysis approach to unravel the immune microenvironment of TB and delineate distinct subtypes within pulmonary TB (PTB) patients. Leveraging functional gene expression signatures (Fges), we identified three PTB subtypes (C1, C2, and C3) characterized by differential immune-inflammatory activity. These subtypes exhibited unique molecular features, functional disparities, and cell infiltration patterns, suggesting varying disease trajectories and treatment responses. A neural network model was developed to predict PTB progression based on a set of biomarker genes, achieving promising accuracy. Notably, despite both genders being affected by PTB, females exhibited a relatively higher risk of deterioration. Additionally, single-cell analysis provided insights into enhanced major histocompatibility complex (MHC) signaling in the rapid clearance of early pathogens in the C3 subgroup. This comprehensive approach offers valuable insights into PTB pathogenesis, facilitating personalized treatment strategies and precision medicine interventions.

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Section: Resultsmentioning

confidence: 99%

Multi-cohort analysis reveals immune subtypes and predictive biomarkers in tuberculosis

Li,

Wang,

Chen

et al. 2024

Sci Rep

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“…Similar mechanism was postulated to be correlated with the reallocation of T lymphocytes in the tissues [ 42 ]. Besides that, M. tuberculosis-induced T lymphocyte apoptosis, hematopoietic dysfunction, and T-cell exhaustion [ 43 ]. While malaria-associated lymphopenia was described to be mainly due to Fas-induced apoptosis [ 44 ], other studies reported no detected apoptosis in the peripheral blood mononuclear cells (PBMCs) [ 45 ].…”

Section: Lymphopeniamentioning

confidence: 99%

SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147

Shouman,

El-Kholy,

Hussien

et al. 2024

Cell Commun Signal

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T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While lymphocytosis indicates an active anti-viral response, lymphopenia is a sign of poor prognosis. T-cells, in essence, rarely express ACE2 receptors, making the cause of cell depletion enigmatic. Moreover, emerging strains posed an immunological challenge, potentially alarming for the next pandemic. Herein, we review how possible indirect and direct key mechanisms could contribute to SARS-CoV-2-associated-lymphopenia. The fundamental mechanism is the inflammatory cytokine storm elicited by viral infection, which alters the host cell metabolism into a more acidic state. This “hyperlactic acidemia” together with the cytokine storm suppresses T-cell proliferation and triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results in a shift from steady-state hematopoiesis to stress hematopoiesis. Even with low ACE2 expression, the presence of cholesterol-rich lipid rafts on activated T-cells may enhance viral entry and syncytia formation. Finally, direct viral infection of lymphocytes may indicate the participation of other receptors or auxiliary proteins on T-cells, that can work alone or in concert with other mechanisms. Therefore, we address the role of CD147―a novel route―for SARS-CoV-2 and its new variants. CD147 is not only expressed on T-cells, but it also interacts with other co-partners to orchestrate various biological processes. Given these features, CD147 is an appealing candidate for viral pathogenicity. Understanding the molecular and cellular mechanisms behind SARS-CoV-2-associated-lymphopenia will aid in the discovery of potential therapeutic targets to improve the resilience of our immune system against this rapidly evolving virus. Graphical Abstract

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“…The correlation between lymphocyte count and TB is a subject of debate. Some researchers report lymphopenia as a prominent feature, especially in severe disease [15], while others note lymphocytosis [16]. Neutrophils and macrophages play a critical role in the initial immune response (innate immunity) against TB by forming granulomas [17].…”

Section: Introductionmentioning

confidence: 99%

Hematological profiles and mortality risk in critically ill and drug-resistant tuberculosis patients: insights from a longitudinal study

Ali,

Wu,

Moazen

et al. 2024

Egypt J Bronchol

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Background While tuberculosis (TB) remains a significant global health threat, data on mortality in critically ill TB patients and those with drug-resistant TB (DR-TB) is limited. This study explores hematological profiles of critically ill TB patients and those with DR-TB, investigating associations with in-hospital and short-term mortality. Methods A longitudinal study of 269 patients with confirmed TB evaluated baseline blood cell counts and indices from medical records. We calculated in-hospital mortality and short-term prognosis, followed by analysis to identify predictors of mortality using hematological parameters. Results One-third of TB patients were critically ill (35.32%) and required intensive care unit (ICU) admission, while 14.5% had DR-TB, more common in females and smokers. Critically ill patients were older and tended to be non-smokers. DR-TB patients exhibited elevated lymphocyte and monocyte counts but lower neutrophil count and blood indices. Critically ill DS-TB patients had lower hemoglobin (Hb) and platelet (PLT) but higher total leucocytes count (TLC) and mean platelet volume (MPV). In-hospital mortality rate was 29.37%, significantly higher in critically ill DS-TB patients (74.74%). In-hospital mortality was 14-fold higher in critically ill DS-TB patients, 11-fold higher in stable DR-TB patients, and 6-fold higher in patients with comorbidities. Decreased Hb, monocyte level, and neutrophil to lymphocyte ratio (NLR) were significantly associated with in-hospital mortality. Predictors of short-term mortality included critical illness and comorbidities. However, the effect of DR-TB on short-term mortality disappeared. Decreasing Hb and TLC, especially neutrophils were significantly linked to short-term mortality. The utility of Hb in discriminating in-hospital and short-term mortality was very good, with AUC values of 78% and 79%, respectively. Cutoff values of less than 10 mg/dL and 9.75 mg/dL showed sensitivity ranging from 71 to 80% and specificity ranging from 75 to 80%, respectively. Conclusion This study provides valuable insights into patients with DR-TB and DS-TB with critically illness. We observed elevated lymphocyte and monocyte counts in DR-TB patients, as well as significant alterations in blood indices in critically ill patients. Importantly, the in-hospital mortality was notably higher in critically ill DS-TB patients, highlighting the importance of early recognition and aggressive management in this subgroup. Specifically, certain blood parameters such as hemoglobin, monocytes, neutrophils, and the NLR were associated with an increased risk of both in-hospital and short-term mortality. Furthermore, our findings underscore the prognostic significance of hematological parameters, particularly in resource-limited settings.

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Possible Mechanisms of Lymphopenia in Severe Tuberculosis

Cited by 3 publications

References 121 publications

Multi-cohort analysis reveals immune subtypes and predictive biomarkers in tuberculosis

Multi-cohort analysis reveals immune subtypes and predictive biomarkers in tuberculosis

SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147

Hematological profiles and mortality risk in critically ill and drug-resistant tuberculosis patients: insights from a longitudinal study

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