Mycobacterium Tuberculosis Infection Research Articles

Cost-effectiveness of diagnostic technologies for mycobacterium tuberculosis infection in India and Brazil.

The economic value of new skin-based tests and blood-based interferon-γ release assays (IGRAs) for tuberculosis (TB) infection is not yet well-established. This study evaluates the cost and cost-effectiveness in two high-burden countries by comparing:(a) new skin-based tests(Diaskintest and Cy-Tb) with the purified protein derivative (PPD)-tuberculin test (TST);(b) IGRAs (Standard E TB-Feron ELISA (TBF))with approved IGRAs (QuantiFERON-TB Gold Plus (QFT-GP)and TSPOT.TB); and (c) the best performing skin-based test with the best performing IGRA) based on cost effectiveness. In this paper, we developed a decision tree model for India and Brazil from a health system perspective. To quantify the effect of parameter variability and uncertainty, we performed both univariate and probabilistic sensitivity analysis. The study findings reveal that among skin-based tests, the Diaskintest is more cost-effective compared to TST-PPD at 22.6 USD and 41.0 USD per correctly diagnosed case of TB infection for Brazil and India, respectively. For blood-based assays, TSPOT.TB outperforms QFT-GP and TBF due to its lower cost and higher effectiveness. When compared with Diaskintest, TSPOT.TB has an incremental cost of approximately 8 USD and 6 USD for India and Brazil respectively but is more effective. The incremental cost-effectiveness ratio (ICER) was 74 USD and 55 USD for India and Brazil, respectively. In summary, while Diaskintest is potentially cost-saving when compared to TSPOT.TB in these two high-burden TB countries but the TSPOT.TB demonstrates higher effectiveness.

The performance of a new rapid interferon gamma release assay based on fluorescence immunochromatography for Mycobacterium tuberculosis infection testing in village doctors in China.

The performance of a new rapid interferon gamma release assay based on fluorescence immunochromatography for Mycobacterium tuberculosis infection testing in village doctors in China.

The cGAS-STING pathway in HIV-1 and Mycobacterium tuberculosis coinfection.

Mycobacterium tuberculosis (M. tuberculosis) infection is the most common opportunistic infection in human immunodeficiency virus-1 (HIV-1)-infected individuals, and the mutual reinforcement of these two pathogens may accelerate disease progression and lead to rapid mortality. Therefore, HIV-1/M. tuberculosis coinfection is one of the major global public health concerns. HIV-1 infection is the greatest risk factor for M. tuberculosis infection and increases the likelihood of endogenous relapse and exogenous reinfection with M. tuberculosis. Moreover, M. tuberculosis further increases HIV-1 replication and the occurrence of chronic immune activation, accelerating the progression of HIV-1 disease. Exploring the pathogenesis of HIV-1/M. tuberculosis coinfections is essential for the development of novel treatments to reduce the global burden of tuberculosis. Innate immunity, which is the first line of host immune defense, plays a critical role in resisting HIV-1 and M. tuberculosis infections. The role of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, which is a major DNA-sensing innate immune signaling pathway, in HIV-1 infection and M. tuberculosis infection has been intensively studied. This paper reviews the role of the cGAS-STING signaling pathway in HIV-1 infection and M. tuberculosis infection and discusses the possible role of this pathway in HIV-1/M. tuberculosis coinfection to provide new insight into the pathogenesis of HIV-1/M. tuberculosis coinfection and the development of novel therapeutic strategies.

Establishment of CD1b-restricted immunity to lipid antigens in the pulmonary response to Mycobacterium tuberculosis infection.

CD1 is an antigen-presenting glycoprotein homologous to MHC I; however, CD1 proteins present lipid rather than peptide antigens. CD1 proteins are well established to present lipid antigens of Mycobacterium tuberculosis (Mtb) to T cells, but understanding the role of CD1-restricted immunity in vivo in response to Mtb infection has been limited by the availability of animal models naturally expressing the CD1 proteins implicated in human response: CD1a, CD1b, and CD1c. Guinea pigs, in contrast to other rodent models, express four CD1b orthologs, and here we utilize the guinea pig to establish the kinetics of gene and protein expression of CD1b orthologs, as well as the Mtb lipid-antigen and CD1b-restricted immune response at the tissue level over the course of Mtb infection. Our results indicate transient upregulation of CD1b expression during the effector phase of adaptive immunity that wanes with disease chronicity. Gene expression indicates that the upregulation of CD1b is the result of transcriptional induction across all CD1b orthologs. We show high CD1b3 expression on B cells, and identify CD1b3 as the predominant CD1b ortholog in pulmonary granuloma lesions. We identify ex vivo cytotoxic activity directed against CD1b that parallels the kinetic changes in CD1b expression in Mtb-infected lungs and spleen. This study confirms that CD1b expression is modulated by Mtb infection in lung and spleen, leading to pulmonary and extrapulmonary CD1b-restricted immunity as a component of the antigen-specific response to Mtb infection.

Effect of CD4 count on Mycobacterium tuberculosis infection rates in people living with HIV: a comparative study in prison and community

To evaluate the impact of the CD4 count on ESAT6-CFP10 (EC) skin test, QuantiFERON-TB Gold In-tube test (QFT) and tuberculin skin test (TST) in a large prison and communities in Jiangsu Province among people living with HIV (PLHIV). Participants in communities were tested with the QFT and EC skin test and in prison were tested with the QFT, TST and EC skin test. A 4-knotted restricted cubic spline fitted for Logistic models was used to explore the cutoff point of CD4 count and the associations between changes in CD4 count and Mycobacterium tuberculosis (M.tb) infection. Among 1,815 PLHIV included, 19.3% (350) were from prisons and 80.7% (1465) were identified through community screenings. M.tb infection rates were 12.2% and 8.3% through QFT and EC tests, respectively. Odd Ratios (ORs) for infection increased with CD4 counts, peaking at 618 cells/mm3 for EC, 392 cells/mm3 for QFT, then plateaued. However, the pattern differed for EC between prison and screening scenarios. In prison settings, M.tb infection increased with CD4 count from 0 to 350 cells/mm3, plateaued until 500 cells/mm3, and then persistently increased. Conversely, for community, ORs decreased until 300 cells/mm3, followed by an increase between 300 and 729 cells/mm3, after which they continued to rise persistently. Our cross-sectional study among PLHIV revealed a higher rate of M.tb infection in prison compared to the community. The relationship between CD4 count and infection became negative after a certain threshold. This pivotal point differed with detection methods, with QFT showing lower CD4 thresholds than EC.

Mycobacterium tuberculosis infection and tuberculosis disease in the first decade of life: a South African birth cohort study

Paediatric tuberculosis leads to more than 200 000 deaths annually. We aimed to investigate the incidence of Mycobacterium tuberculosis infection and tuberculosis disease in the first decade of life in the Drakenstein Child Health Study (DCHS), a South African cohort in a community with high tuberculosis and HIV incidence. In this prospective birth cohort study, we enrolled pregnant women aged 18 years or older who were between 20 and 28 weeks' of gestation in a peri-urban setting outside of Cape Town, South Africa. We followed up their children for tuberculosis until age 10 years. To measure M tuberculosis infection tuberculin skin tests were administered to children at age 6 months, 12 months, and then annually in children with a negative test, and at the time of a lower respiratory tract infection. Tuberculin skin test conversion was defined by an induration reaction of 10 mm or more. To measure tuberculosis disease, active surveillance was done throughout follow-up. Each episode of presumed tuberculosis disease was investigated using sputum induction, tested with Xpert MTB/RIF and liquid culture for M tuberculosis. Survival analyses were performed and multivariable Cox regression was used to measure factors associated with M tuberculosis infection or disease. Between March 5, 2012, and March 31, 2015, 1137 women and their 1143 children (248 [21·7%] of 1143 children were HIV-exposed, two [0·2%] children with HIV) were included in the analysis. Children were followed up for 8870 person-years (median follow-up 9·1 years [IQR 8·2-10·2]). The annual risk of tuberculin conversion during follow-up was 6·6 infections per 100 person-years (95% CI 5·8-7·3) but ranged from 4-9 infections per 100 person-years over the follow-up period. 98 children developed tuberculosis (1105 cases per 100 000 person-years; 95% CI 906-1347). The cumulative hazard of tuberculin conversion was 36% (95% CI 32-41) at age 8 years and the cumulative hazard of tuberculosis disease was 10% (8-12) at age 10 years. Preventive treatment was associated with a reduction in tuberculosis disease among children who had tuberculin conversion (adjusted hazard ratio 0·23 [95% CI 0·12-0·47]). Most cases of tuberculosis disease (78 [79%; 95% CI 69-86] of 98 children) occurred among children who had tuberculin skin test conversion but were not administered preventive treatment. In this prospective South African birth cohort, M tuberculosis transmission was consistently high throughout the first decade of life leading to approximately 10% of children developing tuberculosis disease. A multipronged approach to decrease paediatric tuberculosis is needed that combines preventive treatment for children at risk, reducing community M tuberculosis transmission, and active case finding. Bill & Melinda Gates Foundation, Medical Research Council South Africa, and National Research Foundation South Africa.

Pathogen and host determinants of extrapulmonary tuberculosis among 1035 patients in Frankfurt am Main, Germany, 2008-2023

ObjectivesExtrapulmonary tuberculosis (EPTB) presents with nonspecific symptoms which can pose a significant diagnostic challenge. Various factors, including age, sex, and HIV status, have been associated with an increased risk of developing EPTB. However, the influence of the lineage of the infecting Mycobacterium tuberculosis complex (Mtbc) strain remains controversial. MethodsBetween 2008 and 2023, comprehensive clinical data from 1035 cases, along with whole genome sequencing (WGS) data of the respective Mtbc strains have been collected. To examine the association between Mtbc lineage and EPTB, we calculated crude and adjusted odds ratios (OR) using logistic regression and performed propensity score matching with a subset of the cohort. ResultsOf the 1035 patients, 272 had exclusively extrapulmonary disease and 138 had both pulmonary and extrapulmonary disease. Patients infected with a lineage 1 strain had the highest odds of developing EPTB in the univariate analysis (OR: 3.30, 95% CI: 1.97-5.49). However, Mtbc lineage was not a significant predictor in the multivariable model, while the odds of developing extrapulmonary disease were higher among patients born in the South-East Asian region (adjusted OR: 6.00, 95% CI: 3.41-10.69) and the Eastern Mediterranean Region (adjusted OR: 5.95, 95% CI: 3.61-9.96) compared to those born in the European region. Further, female sex and age were significant positive predictors for EPTB. ConclusionsOur results demonstrate that host factors, such as geographic origin, age and sex are stronger predictors for EPTB than infection with a Mtbc strain of a particular lineage. Further investigation of this host-pathogen interaction is needed.

Whole blood transcriptional profiles and the pathogenesis of tuberculous meningitis.

Mortality and morbidity from tuberculous meningitis (TBM) are common, primarily due to inflammatory response to Mycobacterium tuberculosis infection, yet the underlying mechanisms remain poorly understood. We aimed to uncover genes and pathways associated with TBM pathogenesis and mortality, and determine the best predictors of death, utilizing whole-blood RNA sequencing from 281 Vietnamese adults with TBM, 295 pulmonary tuberculosis (PTB), and 30 healthy controls. Through weighted gene co-expression network analysis, we identified hub genes and pathways linked to TBM severity and mortality, with a consensus analysis revealing distinct patterns between HIV-positive and HIV-negative individuals. We employed multivariate elastic-net Cox regression to select candidate predictors of death, then logistic regression and internal bootstrap validation to choose best predictors. Increased neutrophil activation and decreased T and B cell activation pathways were associated with TBM mortality. Among HIV-positive individuals, mortality associated with increased angiogenesis, while HIV-negative individuals exhibited elevated TNF signaling and impaired extracellular matrix organization. Four hub genes-MCEMP1, NELL2, ZNF354C, and CD4-were strong TBM mortality predictors. These findings indicate that TBM induces a systemic inflammatory response similar to PTB, highlighting critical genes and pathways related to death, offering insights for potential therapeutic targets alongside a novel four-gene biomarker for predicting outcomes.

Whole blood transcriptional profiles and the pathogenesis of tuberculous meningitis

Mortality and morbidity from tuberculous meningitis (TBM) are common, primarily due to inflammatory response to Mycobacterium tuberculosis infection, yet the underlying mechanisms remain poorly understood. We aimed to uncover genes and pathways associated with TBM pathogenesis and mortality, and determine the best predictors of death, utilizing whole-blood RNA sequencing from 281 Vietnamese adults with TBM, 295 pulmonary tuberculosis (PTB), and 30 healthy controls. Through weighted gene co-expression network analysis, we identified hub genes and pathways linked to TBM severity and mortality, with a consensus analysis revealing distinct patterns between HIV-positive and HIV-negative individuals. We employed multivariate elastic-net Cox regression to select candidate predictors of death, then logistic regression and internal bootstrap validation to choose best predictors. Increased neutrophil activation and decreased T and B cell activation pathways were associated with TBM mortality. Among HIV-positive individuals, mortality associated with increased angiogenesis, while HIV-negative individuals exhibited elevated TNF signaling and impaired extracellular matrix organization. Four hub genes—MCEMP1, NELL2, ZNF354C, and CD4—were strong TBM mortality predictors. These findings indicate that TBM induces a systemic inflammatory response similar to PTB, highlighting critical genes and pathways related to death, offering insights for potential therapeutic targets alongside a novel four-gene biomarker for predicting outcomes.

Toxoplasma gondii macrophage migration inhibitory factor shows anti-Mycobacterium tuberculosis potential via AZIN1/STAT1 interaction.

Mycobacterium tuberculosis (MTB) is a pathogenic bacterium, belonging to the family Mycobacteriaceae, that causes tuberculosis (TB). Toxoplasma gondii macrophage migration inhibitory factor (TgMIF), a protein homolog of macrophage migration inhibitory factor, has been explored for its potential to modulate immune responses during MTB infections. We observed that TgMIF that interacts with CD74, antizyme inhibitor 1 (AZIN1), and signal transducer and activator of transcription 1 (STAT1) modulates endocytosis, restoration of mitochondrial function, and macrophage polarization, respectively. These interactions promote therapeutic efficacy in mice infected with MTB, thereby presenting a potential route to host-directed therapy development. Furthermore, TgMIF, in combination with first-line TB drugs, significantly inhibited drug-resistant MTB strains, including multidrug-resistant TB. These results demonstrate that TgMIF is potentially a multifaceted therapeutic agent against TB, acting through immune modulation, enhancement of mitochondrial function, and dependent on STAT1 and AZIN1 pathways.

Gut microbiota: a crucial player in the combat against tuberculosis.

The mammalian gastrointestinal tract quickly becomes densely populated with foreign microorganisms shortly after birth, thereby establishing a lifelong presence of a microbial community. These commensal gut microbiota serve various functions, such as providing nutrients, processing ingested compounds, maintaining gut homeostasis, and shaping the intestinal structure in the host. Dysbiosis, which is characterized by an imbalance in the microbial community, is closely linked to numerous human ailments and has recently emerged as a key factor in health prognosis. Tuberculosis (TB), a highly contagious and potentially fatal disease, presents a pressing need for improved methods of prevention, diagnosis, and treatment strategies. Thus, we aim to explore the latest developments on how the host's immune defenses, inflammatory responses, metabolic pathways, and nutritional status collectively impact the host's susceptibility to or resilience against Mycobacterium tuberculosis infection. The review addresses how the fluctuations in the gut microbiota not only affect the equilibrium of these physiological processes but also indirectly influence the host's capacity to resist M. tuberculosis. This work highlights the central role of the gut microbiota in the host-microbe interactions and provides novel insights for the advancement of preventative and therapeutic approaches against tuberculosis.

The progress of Mycobacterium tuberculosis drug targets.

Tuberculosis (TB) has been troubling humans for hundreds of years, is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, Mtb can infect almost all organs of the body and is one of the deadly infectious diseases in the world. At present, the first-line treatment regimen has a long treatment cycle and is prone to multiple drug resistance. Anti-tuberculosis drugs and latent tuberculosis infection (LTBI) resistance are increasing year by year, and new targets and new bioactive compounds are urgently needed to treat this disease. This review focuses on the latest reported anti-TB drug targets and related compounds in recent years, reviews the current TB drug regimen and major defects, outlines the key drug targets developed to date in Mtb, and the current situation of newly discovered anti-TB resistant forms of drugs. To provide a reference for the research and development of new anti-TB drugs and bring new treatment strategies for TB patients.

Hubungan Kepatuhan Minum Obat dengan Kualitas Hidup Pasien TB Paru di Puskesmas Mustika Jaya Tahun 2023

Pulmonary tuberculosis is caused by a Mycobacterium tuberculosis infection, which attacks the lungs and causes respiratory issues such as chronic cough and shortness of breath. This study aims to analyze the relationship between medication adherence and the quality of life of pulmonary TB patients at Mustika Jaya Public Health Center in 2023. The research design is observational analytic with a cross-sectional approach, using a sample of 78 TB patients selected through purposive sampling. The instruments used include the Morisky Medication Adherence Scale (MMAS-8) for medication adherence and the WHOQOL-BREF questionnaire for quality of life assessment. Chi-square test results showed a significant relationship between medication adherence and quality of life, with a p-value of 0.00. A total of 51.7% of patients who adhered to their medication had a good quality of life. In conclusion, there is a significant positive relationship between medication adherence and quality of life in pulmonary TB patients at Mustika Jaya Health Center in 2023.

The divergent outcome of IL-4Rα signalling on Foxp3 T regulatory cells in listeriosis and tuberculosis.

Forkhead box P3 (Foxp3) T regulatory cells are critical for maintaining self-tolerance, immune homeostasis, and regulating the immune system. We investigated interleukin-4 receptor alpha (IL-4Rα) signalling on T regulatory cells (Tregs) during Listeria monocytogenes (L. monocytogenes) infection using a mouse model on a BALB/c background, specifically with IL-4Rα knockdown in Tregs (Foxp3creIL-4Rα-/lox). We showed an impairment of Treg responses, along with a decreased bacterial burden and diminished tissue pathology in the liver and spleen, which translated into better survival. Mechanistically, we observed an enhancement of the Th1 signature, characterised by increased expression of the T-bet transcription factor and a greater number of effector T cells producing IFN-γ, IL-2 following ex-vivo stimulation with heat-killed L. monocytogenes in Foxp3creIL-4Rα-/lox mice. Furthermore, CD8 T cells from Foxp3creIL-4Rα-/lox mice displayed increased cytotoxicity (Granzyme-B) with higher proliferation capacity (Ki-67), better survival (Bcl-2) with concomitant reduced apoptosis (activated caspase 3). In contrast to L. monocytogenes, Foxp3creIL-4Rα-/lox mice displayed similar bacterial burdens, lung pathology and survival during Mycobacterium tuberculosis (M. tuberculosis) infection, despite increased T cell numbers and IFN-γ, TNF and IL-17 production. Our results demonstrated that the diminished IL-4Rα signalling on Foxp3+ T regulatory cells resulted in a loss of their functionality, leading to survival benefits in listeriosis but not in tuberculosis.

LncRNA SNHG16 Inhibits Intracellular M. tuberculosis Growth Involving Cathelicidin Pathway, Autophagy, and Effector Cytokines Production.

Long noncoding small nucleolar RNA (LncRNA) host gene 16 (SNHG16) is associated with certain diseases, including cancers. However, its role and mechanism in Mycobacterium tuberculosis (Mtb) infection remain unclear. Here, we demonstrated that SNHG16 expression levels were suppressed in peripheral blood mononuclear cells (PBMCs) and CD14+ monocytes of tuberculosis (TB) patients. SNHG16 was up-regulated by acute Mtb infection of PBMCs from healthy control (HC) subjects. Such TB suppression of SNHG16 was consistent with an immunosuppressive-like state driven by IL-10 signaling as seen in TB patients. Notably, SNHG16 limited Mtb growth in macrophages/monocytes through autophagy and vitamin D receptor (VDR)-dependent cathelicidin (CAMP) antimicrobial pathways. Concurrently, SNHG16 was highly expressed in lymphocytes, including CD8+ and Vγ2 Vδ2 T-cell subsets in HCs. SNHG16 overexpression in lymphocytes allowed them to control Mtb infection in macrophages, and SNHG16 epigenetically increased the expression of anti-Mtb effector cytokines in lymphocytes by developing more accessible chromatin states in gene loci encoding IFN-γ, TNF-α, and Granzyme B. Furthermore, the adoptive transfer of SNHG16-overexpressing human PBMCs into Mtb-infected SCID mice conferred protective immunity against Mtb infection. Thus, SNHG16 drove the induction of pleiotropic effector functions that inhibited intracellular Mtb growth in vitro and in vivo, serving as an immunotherapy target in TB.

Differential requirement of formyl peptide receptor 1 in macrophages and neutrophils in the host defense against Mycobacterium tuberculosis Infection

Formyl peptide receptors (FPR), part of the G-protein coupled receptor superfamily, are pivotal in directing phagocyte migration towards chemotactic signals from bacteria and host tissues. Although their roles in acute bacterial infections are well-documented, their involvement in immunity against tuberculosis (TB) remains unexplored. Here, we investigate the functions of Fpr1 and Fpr2 in defense against Mycobacterium tuberculosis (Mtb), the causative agent of TB. Elevated levels of Fpr1 and Fpr2 were found in the lungs of mice, rabbits and peripheral blood of humans infected with Mtb, suggesting a crucial role in the immune response. The effects of Fpr1 and Fpr2 deletion on bacterial load, lung damage, and cellular inflammation were assessed in a murine TB model utilizing hypervirulent strain of Mtb from the W-Beijing lineage. While Fpr2 deletion had no impact on disease outcome, Fpr1-deficient mice demonstrated improved bacterial control, especially by macrophages. Bone marrow-derived macrophages from these Fpr1−/− mice exhibited an enhanced ability to contain bacterial growth over time. Contrarily, treating genetically susceptible mice with Fpr1-specific inhibitors caused impaired early bacterial control, corresponding with increased Mtb persistence in necrotic neutrophils. Furthermore, ex vivo assays revealed that Fpr1−/− neutrophils were unable to restrain Mtb growth, indicating a differential function of Fpr1 among myeloid cells. These findings highlight the distinct and complex roles of Fpr1 in myeloid cell-mediated immunity against Mtb infection, underscoring the need for further research into these mechanisms for a better understanding of TB immunity.

Nanomaterial-mediated host directed therapy of tuberculosis by manipulating macrophage autophagy.

Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a major public health issue worldwide. Mtb has developed complicated strategies to inhibit the immunological clearance of host cells, which significantly promote TB epidemic and weaken the anti-TB treatments. Host-directed therapy (HDT) is a novel approach in the field of anti-infection for overcoming antimicrobial resistance by enhancing the antimicrobial activities of phagocytes through phagosomal maturation, autophagy and antimicrobial peptides. Autophagy, a highly conserved cellular event within eukaryotic cells that is effective against a variety of bacterial infections, has been shown to play a protective role in host defense against Mtb. In recent decades, the introduction of nanomaterials into medical fields open up a new scene for novel therapeutics with enhanced efficiency and safety against different diseases. The active modification of nanomaterials not only allows their attractive targeting effects against the host cells, but also introduce the potential to regulate the host anti-TB immunological mechanisms, such as apoptosis, autophagy or macrophage polarization. In this review, we introduced the mechanisms of host cell autophagy for intracellular Mtb clearance, and how functional nanomaterials regulate autophagy for disease treatment. Moreover, we summarized the recent advances of nanomaterials for autophagy regulations as novel HDT strategies for anti-TB treatment, which may benefit the development of more effective anti-TB treatments.

Advancing Roles and Therapeutic Potentials of Pyroptosis in Host Immune Defenses against Tuberculosis.

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, remains a deadly global public health burden. The use of recommended drug combinations in clinic has seen an increasing prevalence of drug-resistant TB, adding to the impediments to global control of TB. Therefore, control of TB and drug-resistant TB has become one of the most pressing issues in global public health, which urges the exploration of potential therapeutic targets in TB and drug-resistant TB. Pyroptosis, a form of programmed cell death characterized by cell swelling and rupture, release of cellular contents and inflammatory responses, has been found to promote pathogen clearance and adopt crucial roles in the control of bacterial infections. It has been demonstrated that Mtb can cause host cell pyroptosis, and these host cells, which are infected by Mtb, can kill Mtb accompanied by pyroptosis, while, at the same time, pyroptosis can also release intracellular Mtb, which may potentially worsen the infection by exacerbating the inflammation. Here, we describe the main pathways of pyroptosis during Mtb infection and summarize the identified effectors of Mtb that regulate pyroptosis to achieve immune evasion. Moreover, we also discuss the potentials of pyroptosis to serve as an anti-TB therapeutic target, with the aim of providing new ideas for the development of TB treatments.

Fatty acid metabolism in neutrophils promotes lung damage and bacterial replication during tuberculosis.

Mycobacterium tuberculosis (Mtb) infection induces a marked influx of neutrophils into the lungs, which intensifies the severity of tuberculosis (TB). The metabolic state of neutrophils significantly influences their functional response during inflammation and interaction with bacterial pathogens. However, the effect of Mtb infection on neutrophil metabolism and its consequent role in TB pathogenesis remain unclear. In this study, we examined the contribution of glycolysis and fatty acid metabolism on neutrophil responses to Mtb HN878 infection using ex-vivo assays and murine infection models. We discover that blocking glycolysis aggravates TB pathology, whereas inhibiting fatty acid oxidation (FAO) yields protective outcomes, including reduced weight loss, immunopathology, and bacterial burden in lung. Intriguingly, FAO inhibition preferentially disrupts the recruitment of a pathogen-permissive immature neutrophil population (Ly6Glo/dim), known to accumulate during TB. Targeting carnitine palmitoyl transferase 1a (Cpt1a)-a crucial enzyme in mitochondrial β-oxidation-either through chemical or genetic methods impairs neutrophils' ability to migrate to infection sites while also enhancing their antimicrobial function. Our findings illuminate the critical influence of neutrophil immunometabolism in TB pathogenesis, suggesting that manipulating fatty acid metabolism presents a novel avenue for host-directed TB therapies by modulating neutrophil functions.

A rare case of intestinal obstruction due to tuberculosis.

A 19-year-old previously healthy patient presented with severe abdominal pain. A contrast-enhanced CT scan identified ileal obstruction and lower left lung lobe changes suggestive of an inflammatory process. Diagnostic laparoscopy revealed ileal distension, hyperemia, and whitish nodules on the serosa. Acid-fast bacilli staining was positive, confirming Mycobacterium tuberculosis infection. The patient improved with a tuberculosis regimen. Intestinal TB often affects the ileocecal area and presents with symptoms like abdominal pain and obstruction. Diagnosis is confirmed by AFB staining, and treatment mirrors pulmonary TB, though surgery may be needed for complications.