Eicosanoid pathways regulate adaptive immunity to Mycobacterium tuberculosis.
The fate of infected macrophages has an essential role in protection against Mycobacterium tuberculosis by regulating innate and adaptive immunity. M. tuberculosis exploits cell necrosis to exit from macrophages and spread. In contrast, apoptosis, which is characterized by an intact plasma membrane, is an innate mechanism that results in lower bacterial viability. Virulent M. tuberculosis inhibits apoptosis and promotes necrotic cell death by inhibiting production of prostaglandin E(2). Here we show that by activating the 5-lipoxygenase pathway, M. tuberculosis not only inhibited apoptosis but also prevented cross-presentation of its antigens by dendritic cells, which impeded the initiation of T cell immunity. Our results explain why T cell priming in response to M. tuberculosis is delayed and emphasize the importance of early immunity.
Divangahi
Maziar
M
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Desjardins
Danielle
D
Nunes-Alves
Cláudio
C
Remold
Heinz G
HG
Behar
Samuel M
SM
D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001094:Arachidonate 5-Lipoxygenase / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007113:Immunity, Innate / Q000276:immunology; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D009336:Necrosis; D015398:Signal Transduction; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D014774:Virulence
D000942:Antigens, Bacterial; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase; D015232:Dinoprostone