Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections

Judith N Mandl, et al. 2008.Nature Medicine 14,1077-1087

Speaker : 陳倩怡                             Time:15:00-16:00 , Dec 31, 2008 Commentator : 王憲威  老師                                                  Place : Room 601

Abstract:

        Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that can lead to acquired immunodeficiency syndrome (AIDS). After HIV infection, turnover rates of CD4+ and CD8+ T cells are elevated, high levels of activation-induced cell death are seen in both T cell subsets independent of their infection by HIV, B cells are polyclonally activated with consequent hypergammaglobulinemia, natural killer (NK) cell activation and turnover is increased and dendritic cell (DC) numbers are diminished in the peripheral blood. To explore how sooty mangabeys avoid aberrant immune activation, the authors developed a comparative experimental infection model in which sooty mangabeys and non-natural rhesus macaque hosts are inoculated with SIVsm obtained directly from a naturally infected sooty mangabey.They found out that limited NK cell expansion in SIV-infected sooty mangabeys , lack of sooty mangabey pDC activation in acute SIV infection . SIV stimulates IFN-alpha production by pDCs via TLR7 and TLR9. Furthermore,chloroquine, an endosome acidification inhibitor that blocks both TLR7 and TLR9 signaling, inhibited SIV-stimulated IFN-alpha secretion to below detection .The greater inhibition of SIV-stimulated type I interferon production with the dual TLR7 and TLR9 inhibitor compared to each single TLR antagonist alone lends support to a possible role for both TLR7 and TLR9 in the recognition of SIV. Thus, SIV, like HIV, requires TLR7, TLR9 or both to induce a type I interferon response in both rhesus macaques and humans. Understanding the commonalities between sooty mangabeys and other natural hosts for nonpathogenic SIV infections may enable us to anticipate the future evolutionary trajectory of human populations in response to the profound selective pressures imposed by the AIDS pandemic.

References:

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