IL-32 and HIV Persistence
The proinflammatory cytokine IL-32, was originally identified in 1992, but until recently has received little attention as a moderator of chronic immune activation. Recent experiments support the hypothesis that IL-32 may be a contributing factor in an immunoregulatory axis that collectively acts as a double-edged sword in lentiviral immunodeficiency infections.
In a recent paper published by the A. Haase group (1), evidence is given that IL-32 may have such a role in countering immune activation and inflammation during HIV-1 infection by promoting immune suppression via the induction of immunosuppressive molecules (IDO and Ig-like transcript 4). An increased expression of IL-32 was demonstrated in both gut and lymph nodes during all stages of HIV infection (from acute HIV infection to full blown AIDS) and was inversely correlated with HIV replication in lymph nodes. Compared with uninfected individuals, levels of IL-32 were significantly increased in both gut and LT during all stages of HIV-1 infection, with the highest IL-32 levels in the acute stage of disease for gut (4.8-fold increase) and AIDS stage of disease for lymph node (5.8-fold increase).
This IL-32 production concerned CD4+ T cells, B cells, macrophages and dendritic cells.
IL-32 is viewed as a double-edged sword suppressing both the immune activation but also the antiviral immune response. IL-32, IDO, ILT4, and TReg cells therefore constitute important components of an immunoregulatory axis designed to counter the pathological effects of chronic immune activation in persistent HIV-1 infection. The price the host pays for these moderating effects are impaired host defences.
In conclusion, during HIV infection IL-32 moderates chronic immune activation to avert associated immunopathology but at the same time dampens the antiviral immune response and thus paradoxically supports HIV-1 replication and viral persistence.
Smith AJ, Toledo CM, Wietgrefe SW, Duan L, Schacker TW, Reilly CS, Haase AT. The Immunosuppressive Role of IL-32 in Lymphatic Tissue during HIV-1 Infection. J Immunol. 2011 Jun 1;186(11):6576-84. Epub 2011 Apr 27.
Key words: Il-32, gut, hiv persistence, hiv reservoirs, lymph node