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Label-Free Quantitative Proteomics Workflow for Discovery-Driven Host-Pathogen Interactions
Published on: October 20, 2020
17 macrophage virulence assays
1Respiratory Systems, Medical Research Centre, Glaxo Wellcome Research and Development, Hertfordshire, UK.
Abstract:
Mycobacterium tuberculosis is a facultative intracellular pathogen, which can survive and replicate within the host macrophage. It is transmitted via the aerosol route, which delivers the bacillus to the alveolus of the lungs. The initial phase of granuloma formation within the lung requires that the bacterium is ingested by alveolar macrophages. Intracellular replication begins and an inflammatory reaction, involving recruitment of mononuclear leukocytes to the site, is initiated. The resultant accumulation of mononuclear leukocytes (mono-cytes, macrophages, and lymphocytes) is known as a granuloma. The growth of the mycobacteria at this stage in the infection is largely intracellular and acid fast bacilli can be visualized within the macrophages of the granuloma (1).
Insights
Mycobacterium tuberculosis, a lung pathogen, survives inside host macrophages. Initial infection involves granuloma formation in the lungs, where the bacteria replicate intracellularly within macrophages.
Area of Science:
- Immunology
- Microbiology
- Pathology
Background:
- Mycobacterium tuberculosis (M. tuberculosis) is a facultative intracellular pathogen.
- M. tuberculosis infection begins through aerosol transmission to the lungs.
- Host macrophages engulf M. tuberculosis, initiating intracellular replication and inflammation.
Purpose of the Study:
- To describe the initial host-pathogen interactions during Mycobacterium tuberculosis infection.
- To elucidate the early stages of granuloma formation in response to M. tuberculosis.
Main Methods:
- Observational study describing the cellular and pathological processes.
- Microscopic visualization of acid-fast bacilli within host macrophages.
Main Results:
- M. tuberculosis resides and replicates within alveolar macrophages.
- Infection triggers an inflammatory response with recruitment of mononuclear leukocytes.
- Accumulation of leukocytes forms granulomas, characteristic of early M. tuberculosis infection.
Conclusions:
- Granuloma formation is a critical early host response to M. tuberculosis.
- Intracellular replication within macrophages is a key feature of early M. tuberculosis pathogenesis.
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