Latent Tuberculosis: Challenges in Diagnosis and Treatment, Perspectives, and the Crucial Role of Biomarkers

Palanivel, Jayanthi; Sounderrajan, Vignesh; Thangam, T.; Rao, Sudhanarayani S.; Harshavardhan, Shakila; Parthasarathy, Krupakar

doi:10.1007/s00284-023-03491-x

Cited by 10 publications

(3 citation statements)

References 60 publications

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“…The current TB diagnostics include culture, smear, GeneXpert MTB/RIF (Xpert), interferon-gamma release assays (IGRAs), imaging examination, etc. However, the traditional detection of growth in bacterial cultures is timeconsuming; the sensitivity of acid-fast staining-based smear diagnostic is low; Xpert is expensive and impractical for widespread clinical use in developing countries although it is rapid and sensitive; IGRAs cannot distinguish between asymptomatic latent TB infection and active TB disease; and the specificity of imaging examination is low (2)(3)(4). Thus, the diagnosis of TB remains challenging.…”

Section: Editorial On the Research Topicmentioning

confidence: 99%

Editorial: Innate and adaptive immunity against tuberculosis infection: diagnostics, vaccines, and therapeutics

Hu,

Shi,

Xie

et al. 2024

Front. Immunol.

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Section: Editorial On the Research Topicmentioning

confidence: 99%

Editorial: Innate and adaptive immunity against tuberculosis infection: diagnostics, vaccines, and therapeutics

Hu,

Shi,

Xie

et al. 2024

Front. Immunol.

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“…The majority of Mtb-infected individuals remain latently infected without clinical signs (LTBI). However, around 10% of the infected patients will develop active TB, especially in conjunction with immunodeficiency caused by malnutrition, immunosuppressive therapy using steroids, or infection with immunosuppressive pathogens 2 . Among these infection with human immunodeficiency virus (HIV) plays a pivotal role, given that immunosuppression is the hallmark of HIV pathogenesis 3 .…”

Section: Introductionmentioning

confidence: 99%

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

Bohórquez,

Adduri,

Ansari

et al. 2024

Preprint

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. Further, co-infections with HIV and Mtb have severe effects in the host, with people infected with HIV being fifteen to twenty-one times more likely to develop active TB. The use of an appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans would be a useful tool for conducting basic and translational research in HIV/Mtb infections. The present study was focused on developing a humanized mouse model for investigations on HIV-Mtb co-infection. Using NSG-SGM3 mice that can engraft human stem cells, our studies showed that they were able to engraft human CD34+ stem cells which then differentiate into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced the development of granulomatous lesions in the lungs, detected by CT scan and histopathology. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Our results suggest that the humanized NSG-SGM3 mice are able to recapitulate the effects of HIV and Mtb infections and co-infection in the human host at pathological, immunological and metabolism levels, providing a dependable small animal model for studying HIV/Mtb co-infection.

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“…The majority of Mtb-infected individuals remain latently infected without clinical signs (LTBI). However, around 10% of the infected patients will develop active TB and cause severe pathology, during primary immunodeficiency states such as defects of IL-12/IFN-g axis, lack of T and B cells in SCID mice (2), and acquired immunodeficiency caused by malnutrition, immunosuppressive therapy using steroids, or infection with immunosuppressive pathogens (3). Among these, human immunodeficiency virus (HIV) plays a pivotal role, given that CD4+ T cell depletion is the hallmark of HIV pathogenesis (4).…”

Section: Introductionmentioning

confidence: 99%

A novel humanized mouse model for HIV and tuberculosis co-infection studies

Bohórquez,

Adduri,

Ansari

et al. 2024

Front. Immunol.

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BackgroundTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. HIV infection decreases CD4+ T cell levels markedly increasing Mtb co-infections. An appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans during co-infection would facilitate basic and translational research in HIV/Mtb infections. Herein, we describe a novel humanized mouse model.MethodsThe irradiated NSG-SGM3 mice were transplanted with human CD34+ hematopoietic stem cells, and the humanization was monitored by staining various immune cell markers for flow cytometry. They were challenged with HIV and/or Mtb, and the CD4+ T cell depletion and HIV viral load were monitored over time. Before necropsy, the live mice were subjected to pulmonary function test and CT scan, and after sacrifice, the lung and spleen homogenates were used to determine Mtb load (CFU) and cytokine/chemokine levels by multiplex assay, and lung sections were analyzed for histopathology. The mouse sera were subjected to metabolomics analysis.ResultsOur humanized NSG-SGM3 mice were able to engraft human CD34+ stem cells, which then differentiated into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced granulomatous lesions in the lungs. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections.ConclusionThe humanized NSG-SGM3 mice are able to recapitulate the pathogenic effects of HIV and Mtb infections and co-infection at the pathological, immunological and metabolism levels and are therefore a reproducible small animal model for studying HIV/Mtb co-infection.

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Latent Tuberculosis: Challenges in Diagnosis and Treatment, Perspectives, and the Crucial Role of Biomarkers

Cited by 10 publications

References 60 publications

Editorial: Innate and adaptive immunity against tuberculosis infection: diagnostics, vaccines, and therapeutics

Editorial: Innate and adaptive immunity against tuberculosis infection: diagnostics, vaccines, and therapeutics

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

A novel humanized mouse model for HIV and tuberculosis co-infection studies

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