Innate immunity controls infections while the adaptive immune response develops. In the absence of T cells, infections that kill the host were thought to result from an uncontrolled infection. However, Kim and colleagues demonstrate here that the adaptive immune response is also necessary to control the innate immune response. They show that host death can result from an uncontrolled innate response that occurs in the absence of an adaptive immune response.
Triggering the innate immune receptor TLR3 with poly(I:C), a double stranded RNA that mimics viruses, produced a destructive and potentially lethal “cytokine storm”. This fatal reaction required Natural Killer (NK) cells and TNF. The figure is a portion of figure 4 showing the response of immune deficient animals: panel e shows that abrogating TNF signaling but not immunoglobulin signaling is protective and panel f shows that NK cell depletion is protective. As the authors note, these findings might be also important for understanding the responses of “individuals with congenital or acquired immune deficiency”.
Kim et al. Nat Med. 2007 Nov;13(10):1248. "Adaptive immune cells temper initial innate responses".
Wednesday, October 31, 2007
Adaptive Control of Innate Immunity
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The lethal effect seems to be mediated by TNF because TNF is increased dramatically in nude mice (fig 2b), blocking TNF with antibodies protects (fig 4c), and as noted in the gloss, mice deficient in TNF receptors are protected (fig 4e). However, the suppressive effect of T cells on TNF accumulation seems weaker than on IFNg (e.g., fig 3a).
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