title: Induction of SerpinB2 and Th1/Th2 modulation by SerpinB2 during lentiviral infections in vivo.
abstract: SerpinB2, also known as plasminogen activator inhibitor type 2, is a major product of activated monocytes/macrophages and is often strongly induced during infection and inflammation; however, its physiological function remains somewhat elusive. Herein we show that SerpinB2 is induced in peripheral blood mononuclear cells following infection of pigtail macaques with CCR5-utilizing (macrophage-tropic) SIVmac239, but not the rapidly pathogenic CXCR4-utilizing (T cell-tropic) SHIVmn229. To investigate the role of SerpinB2 in lentiviral infections, SerpinB2(-/-) mice were infected with EcoHIV, a chimeric HIV in which HIV gp120 has been replaced with gp80 from ecotropic murine leukemia virus. EcoHIV infected SerpinB2(-/-) mice produced significantly lower anti-gag IgG1 antibody titres than infected SerpinB2(+/+) mice, and showed slightly delayed clearance of EcoHIV. Analyses of published microarray studies showed significantly higher levels of SerpinB2 mRNA in monocytes from HIV-1 infected patients when compared with uninfected controls, as well as a significant negative correlation between SerpinB2 and T-bet mRNA levels in peripheral blood mononuclear cells. These data illustrate that SerpinB2 can be induced by lentiviral infection in vivo and support the emerging notion that a physiological role of SerpinB2 is modulation of Th1/Th2 responses.
authors: Department of Immunology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors: Lee D
authors: LD
authors: Major
authors: Thomas S
authors: TS
authors: Partridge
authors: Joy
authors: J
authors: Gardner
authors: Stephen J
authors: SJ
authors: Kent
authors: Robert
authors: R
authors: de Rose
authors: Andreas
authors: A
authors: Suhrbier
authors: Wayne A
authors: WA
authors: Schroder
mesh_terms: D000818:Animals; D002465:Cell Movement; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016180:Lentivirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008254:Macaca nemestrina / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D017396:Plasminogen Activator Inhibitor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D007074:Immunoglobulin G; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger