Elevated CD40 ligand silences α interferon production in an HIV-related immune reconstitution inflammatory syndrome

摘要

The immune reconstitution inflammatory syndrome (IRIS) occurs in about 10% of HIV-1-infected patients at a median of 12 weeks upon initiation of antiretroviral therapy [11. Low baseline CD4+ T-cell counts predispose for the occurrence of opportunistic infections like genital herpes, warts, herpes zoster, myco-bacterial infections, and Kaposi's sarcoma [1]. Infections with herpes simplex virus type 2 (HSV-2) are most prevalent. The lesions can be treated with aciclovir and imiquimod, an agonist of Toll-like receptor (TLR) 7, but occasionally proliferate to an extensive verrucous mass [2-5]. Imiquimod targets plasmacytoid dendritic cells (PDC), the major producers of type I interferons (IFNs), which are recruited from the peripheral blood to the site of inflammation [6]. So far, it is unclear why IRIS patients develop opportunistic infections despite rapid CD4+ T-cell recovery.