Cytosolic phospholipase A2 enzymes are not required by mouse bone marrow-derived macrophages for the control of Mycobacterium tuberculosis in vitro

During the course of infection Mycobacterium tuberculosis predominantly resides within macrophages, where it encounters and is often able to resist the antibacterial mechanisms of the host. In this study, we assessed the role of macrophage phospholipases A(2) (PLA(2)S) in defense against M. tuberculosis. Mouse bone marrow-derived macrophages (BMDMs) expressed cPLA(2)-IVA, cPLA(2)-IVB, iPLA(2)-VI, sPLA(2)-IIE, and sPLA(2)-XIIA. The expression of cPLA(2)-IVA was increased in response to M. tuberculosis, gamma interferon, or their combination, and cPLA(2)-IVA mediated the release of arachidonic acid, which was stimulated by M. tuberculosis in activated, but not unactivated, macrophages. We confirmed that arachidonic acid is highly mycobactericidal in a concentration- and pH-dependent manner in vitro. However, when M. tuberculosis-infected macrophages were treated with PLA(2) inhibitors, intracellular survival of M. tuberculosis was not affected, even in inducible nitric oxide synthase-deficient macrophages, in which a major bactericidal mechanism is removed. Moreover, intracellular survival of M. tuberculosis was similar in cPLA(2)-IVA-deficient and wild-type macrophages. Our results demonstrate that the cytosolic PLA(2)s are not required by murine BMDMs to kill M. tuberculosis.