An Enzyme That Inactivates the Inflammatory Mediator Leukotriene B-4 Restricts Mycobacterial Infection

作者：Tobin David M^*; Roca Francisco J; Ray John P; Ko Dennis C; Ramakrishnan Lalita

来源：PLos One, 2013, 8(7): e67828.

DOI：10.1371/journal.pone.0067828

While tuberculosis susceptibility has historically been ascribed to failed inflammation, it is now known that an excess of leukotriene A(4) hydrolase (LTA4H), which catalyzes the final step in leukotriene B-4 (LTB4) synthesis, produces a hyperinflammatory state and tuberculosis susceptibility. Here we show that the LTB4-inactivating enzyme leukotriene B-4 dehydrogenase/prostaglandin reductase 1 (LTB4DH/PTGR1) restricts inflammation and independently confers resistance to tuberculous infection. LTB4DH overexpression counters the susceptibility resulting from LTA4H excess while ltb4dh-deficient animals can be rescued pharmacologically by LTB4 receptor antagonists. These data place LTB4DH as a key modulator of TB susceptibility and suggest new tuberculosis therapeutic strategies.

• 出版日期2013-7-11