4.5 Review

Clinical manifestations and immune response to tuberculosis

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Summary: Emerging and re-emerging bacterial infections pose a serious threat to human and animal health, especially those caused by intracellular bacteria. Current treatment methods involve narrow-spectrum antibiotics, but FDA-approved vaccines for obligate intracellular bacterial infections are lacking. However, various types of vaccines are currently being tested in clinical trials, including live, attenuated, subunit, killed whole cell, nano-based, and DNA vaccines.

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A Structural View at Vaccine Development against M. tuberculosis

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Summary: Tuberculosis remains the leading infectious bacterial cause of death worldwide. Developing a new vaccine with better coverage than the current BCG vaccine is vital to stop its spread. Structural Vaccinology and the development of vaccine adjuvants can enhance the immunostimulating effects of subunit vaccines, accelerating the development of a safer and more effective tuberculosis vaccine.
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An RNA-Based Vaccine Platform for Use against Mycobacterium tuberculosis

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Summary: In this study, two delivery platforms were used to assess the efficacy of prophylactic vaccines against M.tb infection in mice. Both protein subunit- and RNA-based vaccines reduced bacterial burden and induced unique immune responses. This suggests that repRNA platforms are a viable option for TB vaccines that contain CD4+ and CD8+ T-cell epitopes.

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Resistance to Mycobacterium tuberculosis infection among highly TB exposed South African gold miners

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Novel In Silico mRNA vaccine design exploiting proteins of M. tuberculosis that modulates host immune responses by inducing epigenetic modifications

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Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity

Meng Wu et al.

Summary: This study investigated the immunological properties of C3 and C3a in Japanese flounder and found that PoC3 is expressed in nine different tissues and upregulated by bacterial challenge. PoC3 in serum can bind to a broad-spectrum of bacteria and directly kill specific pathogens. Knocking down PoC3 expression significantly decreases complement activity and increases bacterial replication in fish tissues. Recombinant PoC3a exhibits binding capacities to bacteria and immune cells, and administration of rPoC3a enhances resistance against bacterial infection.

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Immunometabolism of Immune Cells in Mucosal Environment Drives Effector Responses against Mycobacterium tuberculosis

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Immune evasion and provocation by Mycobacterium tuberculosis

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TREM2 Promotes Immune Evasion by Mycobacterium tuberculosis in Human Macrophages

Ankita Dabla et al.

Summary: Mycobacterium tuberculosis, the causative agent for tuberculosis, binds to TREM2, an immunomodulatory receptor on macrophages, to facilitate a silent mode of entry and intracellular survival. TREM2 upregulation inhibits reactive oxygen species (ROS) and proinflammatory cytokine production, promoting mycobacterial survival within infected macrophages. Targeting TREM2 could be a promising strategy for novel treatments against M. tuberculosis infection.
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The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure

Shogo Ito et al.

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NATURE COMMUNICATIONS (2022)

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Mycobacterium tuberculosis PPE18 protein inhibits MHC class II antigen presentation and B cell response in mice

Komal Dolasia et al.

Summary: PPE18 protein inhibits MHC class II-mediated antigen presentation by macrophages, leading to decreased activation of CD4 T cells and compromised adaptive immune responses. This study sheds light on the host-pathogen interaction and potential therapeutic strategies targeting PPE18.

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Efficient 5-OP-RU-Induced Enrichment of Mucosa-Associated Invariant T Cells in the Murine Lung Does Not Enhance Control of Aerosol Mycobacterium tuberculosis Infection

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Summary: This study tested the impact of a MATT cell priming strategy on mice infected with aerosol Mycobacterium tuberculosis and found that although MATT cells could rapidly activate and expand in the lung after M. tuberculosis exposure, they were not able to restrict M. tuberculosis growth.

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Summary: The study found that MAIT cells mount minimal responses following Mtb infection, but MAIT cell expansion during chronic infection can reduce bacterial loads. The 5-OP-RU vaccination failed to protect against Mtb challenge, but MAIT cells play a role in delaying T cell priming.

MUCOSAL IMMUNOLOGY (2021)

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Heena Jagatia et al.

Summary: The complement system plays a crucial role in orchestrating immune responses against Mycobacterium tuberculosis, activating different pathways to clear the pathogen. However, the bacteria can persist and evade clearance within macrophages, leading to the formation of granulomas which aim to contain the infection while sacrificing host tissue. The full extent of complement system involvement during M. tuberculosis infection is still not fully understood, but research is ongoing to uncover its contribution.

MEDICINA-LITHUANIA (2021)

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Central nervous system tuberculosis

Sofiati Dian et al.

Summary: Recent studies in the field of CNS-TB have focused largely on TB meningitis. The outcome may improve by optimizing treatment dosing, but this needs to be confirmed in clinical trials. Due to the important role of inflammation, these trials should be used as the platform to study the inflammatory and metabolomic responses, which could improve understanding of the biology of this disease and improve patient outlook by enabling individualized host-directed therapy.

CURRENT OPINION IN NEUROLOGY (2021)

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Paula Ruibal et al.

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Edward B. Irvine et al.

Summary: Alter and colleagues demonstrate that IgM titers in plasma and bronchoalveolar lavage fluid are markers of reduced Mtb burden in rhesus macaques vaccinated intravenously with Bacille Calmette-Guerin. This study suggests the potential importance of IgM responses as a marker and mediator of protection against TB, highlighting the superior antibody responses induced by intravenous BCG compared to traditional intradermal administration.

NATURE IMMUNOLOGY (2021)

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Maunank Shah et al.

Summary: Persons with risk factors for Mycobacterium tuberculosis exposure or progression to tuberculosis disease should be tested and treated if necessary. Preferred LTBI treatment options include rifampin-based regimens for a specified duration. Screening for risk factors and LTBI testing are crucial for prevention and treatment of tuberculosis disease.

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Summary: In latent tuberculosis, individuals with diabetes mellitus or pre-diabetes, as well as non-diabetes comorbidities, show significantly reduced expression of cytokines, cytotoxic factors, and immune markers in gamma-delta T cells upon stimulation with specific antigens.

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A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis

Stephanie Fischinger et al.

Summary: South Africa has the highest prevalence of HIV and tuberculosis co-infection globally, with HIV infected individuals having a greater likelihood of developing recurrent TB. This study investigated the humoral response in HIV co-infected individuals with and without recurrent TB, finding differences in antibody profiles, particularly decreased Mtb-antigen specific IgG3 titers in individuals with recurrent TB. These findings suggest a potential role for Mtb-specific IgG3 responses as biomarkers or mediators of protective immunity against Mtb recurrence.

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Early Clearance of Mycobacterium tuberculosis Is Associated With Increased Innate Immune Responses

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Antibody Fc Glycosylation Discriminates Between Latent and Active Tuberculosis

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PD-1-expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

Jing Jiang et al.

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Michael E. Urbanowski et al.

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Ioannis Mitroulis et al.

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Jane A. Shaw et al.

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Elouise E. Kroon et al.

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Sanjay Gambhir et al.

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Hao Li et al.

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Ignacio Duarte

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Christophe J. Queval et al.

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Eric Warren et al.

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Andre A. Figueiredo et al.

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Siddharth Yadav et al.

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Central Nervous System Tuberculosis

John M. Leonard

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A Functional Role for Antibodies in Tuberculosis

Lenette L. Lu et al.

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Tania O. Crisan et al.

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A polymorphism in human CD1A is associated with susceptibility to tuberculosis

C. Seshadri et al.

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Dynamic Modulation of Innate Immune Response by Varying Dosages of Lipopolysaccharide (LPS) in Human Monocytic Cells

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Evasion of Innate and Adaptive Immunity by Mycobacterium tuberculosis

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MICROBIOLOGY SPECTRUM (2014)

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CXCR5+ T helper cells mediate protective immunity against tuberculosis

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The Tuberculous Granuloma: An Unsuccessful Host Defence Mechanism Providing a Safety Shelter for the Bacteria?

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A Novel Human IgA Monoclonal Antibody Protects against Tuberculosis

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Initiation and regulation of T-cell responses in tuberculosis

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CD4+ Regulatory T Cells in a Cynomolgus Macaque Model of Mycobacterium tuberculosis Infection

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Human Mucosal Associated Invariant T Cells Detect Bacterially Infected Cells

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Multiple routes of complement activation by Mycobacterium bovis BCG

Maria V. Carroll et al.

MOLECULAR IMMUNOLOGY (2009)

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Innate and adaptive immune responses to human Mycobacterium tuberculosis infection

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TUBERCULOSIS (2009)

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Fleischner Society: Glossary of terms tor thoracic imaging

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Life and death in the granuloma: immunopathology of tuberculosis

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Protein kinase G from pathogenic mycobacteria promotes survival within macrophages

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Adjuvant corticosteroids for tuberculous pericarditis: promising, but not proven

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How can immunology contribute to the control of tuberculosis?

SHE Kaufmann

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Cytolytic T cells in the immune response to Mycobacterium tuberculosis

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