Lysosomal phospholipase A2: A novel player in host immunity to Mycobacterium tuberculosis
Open accessAbstract
Phospholipases catalyze the cleavage of membrane phospholipids into smaller bioactive molecules. The lysosomal phospholipase A 2 (LPLA 2) is specifically expressed in macrophages. LPLA 2 gene deletion in mice causes lysosomal phospholipid accumulation in tissue macrophages leading to phospholipidosis. This phenotype becomes most prominent in alveolar macrophages where LPLA 2 contributes to surfactant phospholipid degradation. High expression of LPLA 2 in alveolar macrophages prompted us to investigate its role in host immunity against the respiratory pathogen Mycobacterium tuberculosis, the causative agent of tuberculosis. Here we report that adaptive immune responses to M. tuberculosis were impaired in LPLA 2 deficient mice. Upon aerosol infection with M. tuberculosis, LPLA 2 deficient mice showed enhanced mycobacterial counts but less lung immunopathology and pulmonary inflammatory responses. Compromised T‐cell priming in the lymph nodes was associated with impaired pulmonary T‐cell recruitment and activation. Together with reduced Th1 type cytokine production, these results indicate that LPLA 2 is indispensable for the induction of adaptive T‐cell immunity to M. tuberculosis. Taken together, we identified an unexpected and novel function of a lysosomal phospholipid‐degrading enzyme.
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Lack of LPLA2 causes enhanced susceptibility to M. tuberculosis and S. typhimurium infection, although a direct microbicidal effect has not yet been found.
“Its lack causes enhanced susceptibility to M. tuberculosis (43) and S. typhimurium infection (S. Renk, G. Graßl, P. Rausch, J. Shayman, BE. Schneider, UE. Schaible, unpublished data), although a direct microbicidal effect has not yet been found.”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [43]
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- Authors
- Schneider, B. E., Behrends, J., Hagens, K., Harmel, N., Shayman, J. A., & Schaible, U. E.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- Research Center Borstel - Leibniz Lung Center (DE)
- University of Michigan (US)
- Corresponding author
- Schaible, Ulrich E.
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2014-06-11
- Volume
- 44
- Issue
- 8
- Pages
- 2394-2404
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W1495139956
- Cited by
- 35
- References
- 31
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 5 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 4
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (Scha 514 2-1)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- lysosomal phospholipase A2, Mycobacterium tuberculosis, tuberculosis, alveolar macrophages, T cell priming, Th1 cytokines, lung inflammation, phospholipidosis, host immunity
- MeSH terms
- Animals, Inflammation, Lung, Lymph Nodes, Lysosomes, Macrophages, Mice, Inbred C57BL, Mycobacterium tuberculosis, T-Lymphocytes, Tuberculosis, Pulmonary, Tumor Necrosis Factor-alpha, Cytokines, Th1 Cells, Mice, Phospholipases A2, Adaptive Immunity
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