Lysosomal phospholipases of macrophages in antimicrobial defence
Final Report Abstract
Infection of LPLA2 deficient mice revealed differential relevance of this enzyme for host responses to Mtb, Spn and Sty. LPLA2 KO mice were more susceptible to Mtb aerosol infection due to reduced inflammatory T helper 1 cell responses. LPLA2 KO mice were also more susceptible to oral St infection when the intestinal microbiota were depleted by antibiotic treatment, which causes local gastroenteritis. In contrast, the courses of either pulmonary Spn infection as well as the systemic typhoid model of Sty infection were comparable between LPLA2 KO and wild type mice. LPLA2 macrophages were similarly able to kill Mtb, Spn and Sty but failed to degrade the residual bacterial membranes. Furthermore, LPLA2 KO macrophages were inefficient activators of CD4 T cells in vitro. PLD4 was identified as putative LPLA1 through lysosomal purification and proteomics. Both, purified and recombinant PLD4 interacted with phospholipid membranes, and exogenous PLD4 expression enhanced LPLA1 activity. However, generation of a PLD4 KO mouse prove to be difficult for so far unknown reasons. This activity is ongoing.
Publications
- 2013 The granuloma in tuberculosis: dynamics of a hostpathogen collusion. Front Immunol 3:411
Ehlers S., Schaible U.E.
- 2014 Immunomagnetic isolation of pathogen-containing phagosomes and apoptotic blebs from primary phagocytes. Curr Protoc Immunol; 105: 14.36.1-14.36.2
Steinhäuser C, Dallenga T, Tchikov V, Schaible UE, Schütze S, Reiling N
(See online at https://doi.org/10.1002/0471142735.im1436s105) - 2014 Lysosomal phospholipase A2: A novel player in host immunity to Mycobacterium tuberculosis. Eur J Immunol. 44(8): 2394-404
Schneider BE, Behrends J, Hagens K, Harmel N, Shayman JA, Schaible UE
(See online at https://doi.org/10.1002/eji.201344383) - 2015. Macrophage defense mechanisms against intracellular bacteria. Immunological Reviews; Vol. 264: 1–23
Weiss G, Schaible UE
(See online at https://doi.org/10.1111/imr.12266)
