title: The immunosuppressive role of IL-32 in lymphatic tissue during HIV-1 infection.
abstract: One pathological hallmark of HIV-1 infection is chronic activation of the immune system, driven, in part, by increased expression of proinflammatory cytokines. The host attempts to counterbalance this prolonged immune activation through compensatory mediators of immune suppression. We recently identified a gene encoding the proinflammatory cytokine IL-32 in microarray studies of HIV-1 infection in lymphatic tissue (LT) and show in this study that increased expression of IL-32 in both gut and LT of HIV-1-infected individuals may have a heretofore unappreciated role as a mediator of immune suppression. We show that: 1) IL-32 expression is increased in CD4(+) T cells, B cells, macrophages, dendritic cells, and epithelial cells in vivo; 2) IL-32 induces the expression of immunosuppressive molecules IDO and Ig-like transcript 4 in immune cells in vitro; and 3) in vivo, IL-32-associated IDO/Ig-like transcript 4 expression in LT macrophages and gut epithelial cells decreases immune activation but also may impair host defenses, supporting productive viral replication, thereby accounting for the correlation between IL-32 levels and HIV-1 replication in LT. Thus, during HIV-1 infection, we propose that 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.
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Smith
authors.forename: Chad M
authors.initials: CM
authors.lastname: Toledo
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wietgrefe
authors.forename: Lijie
authors.initials: L
authors.lastname: Duan
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Schacker
authors.forename: Cavan S
authors.initials: CS
authors.lastname: Reilly
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
mesh_terms: D000328:Adult; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000378:metabolism / Q000821:virology; D017403:In Situ Hybridization; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012367:RNA, Viral / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012007:Rectum / Q000276:immunology / Q000378:metabolism / Q000821:virology; D013997:Time Factors; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: C496971:IL32 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007378:Interleukins; C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D011971:Receptors, Immunologic