Sex differences in the Toll-like receptor–mediated response of plasmacytoid dendritic cells to HIV-1

Angela M., et al. 2009. Nat. Med. 15, 955-959

Speaker: Jhen-Yu Ke (柯貞妤)                                        Time:13:00~14:00; Oct. 7, 2009

Commentator: Dr. Yea-Lih Lin (林雅俐 老師)            Place: Room 601

Abstract:

Viral infections have been shown to affect women and men differently¹. For example, marked differences between gender are reported in HIV-1 disease progression¹. Women with untreated HIV tend to develop AIDS faster than men with comparable levels of HIV-1 replication². In this paper, the authors showed that plasmacytoid dendritic cells (pDCs) with Toll-like receptor 7 (TLR7) derived from women produced significantly more interferon-alpha (IFN-alpha) in response to HIV-1 than pDCs derived from men. IFN-alpha is an immune-stimulating protein resulting in stronger secondary activation of CD8⁺ T cells. Moreover, this study showed that HIV-infected women who had not yet received treatment had more activated CD8⁺ T cells than men with comparable amount of virus. The expression of immune activation markers on CD8⁺ T cells has been shown to independently predict the rate of HIV-1 disease progression³. This enhanced immune activation in women can explain the clinical observation reported previously that women have a higher risk for HIV-1 disease progression than men during chronic infection at a given HIV-1 viral load. Based on this study, regulation of the TLR7 signaling pathway in pDCs might be an alternative approach for treatment of HIV-1.

References:

1.      Fish, E.N. et al. 2008. The X-files in immunity: sex-based differences predispose immune responses. Nat. Rev. Immunol. 8, 737-744

2.      Farzadegan, H. et al. 1998. Sex differences in HIV-1 viral load and progression to AIDS. Lancet. 352, 1510-1514

3.      Fahey, J.L. et al. 1998. Prognostic significance of plasma markers of immune activation, HIV viral load and CD4 T-cell measurements. AIDS 12, 1581-1590