Lysosomal phospholipase A2: a novel player in host immunity to Mycobacterium tuberculosis.
Phospholipases catalyze the cleavage of membrane phospholipids into smaller bioactive molecules. The lysosomal phospholipase A2 (LPLA2 ) is specifically expressed in macrophages. LPLA2 gene deletion in mice causes lysosomal phospholipid accumulation in tissue macrophages leading to phospholipidosis. This phenotype becomes most prominent in alveolar macrophages where LPLA2 contributes to surfactant phospholipid degradation. High expression of LPLA2 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 LPLA2 deficient mice. Upon aerosol infection with M. tuberculosis, LPLA2 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 LPLA2 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.
Department of Molecular Infection Biology, Cellular Microbiology, Research Center Borstel, Borstel, Germany; Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Bianca E
BE
Schneider
Jochen
J
Behrends
Kristine
K
Hagens
Nadine
N
Harmel
James A
JA
Shayman
Ulrich E
UE
Schaible
D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008247:Lysosomes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D054467:Phospholipases A2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000201:enzymology* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D054467:Phospholipases A2
Immunity; Macrophages; Phospholipase; T cells; Tuberculosis