title: Altered bone marrow dendritic cell cytokine production to toll-like receptor and CD40 ligation during chronic feline immunodeficiency virus infection.
abstract: Impaired dendritic cell (DC) function is thought to be central to human immunodeficiency virus-associated immunodeficiency. In this study, we examined the effect of chronic feline immunodeficiency virus (FIV) infection on DC cytokine production in response to microbial and T-cell stimulation. Cytokine production after either Toll-like receptor (TLR) or CD40 ligation in bone marrow-derived DCs (BM-DCs) was measured in naïve and chronically FIV-infected cats. The BM-DCs were stimulated with ligands to TLR-2, -3, -4, -7 and -9 or cocultured with 3T3 cells expressing feline CD40 ligand. Ligation of TLR-4 and TLR-9 in BM-DCs from infected cats resulted in a significant decrease in the ratio of interleukin-12 (IL-12) to IL-10. Conversely, TLR-7 ligation produced a significant increase in the IL-12 : IL-10 ratio in BM-DCs from infected cats. No difference was noted for TLR-3 ligation. RNA expression levels of TLR-2, -3, -4, -7 and -9 were not significantly altered by FIV infection. CD40 ligation significantly elevated both IL-10 and IL-12 messenger RNA production but did not alter the IL-12 : IL-10 ratio. Chronic FIV infection alters the ratio of immunoregulatory cytokines produced by BM-DCs in response to certain pathogen-derived signals, which is probably relevant to the increased risk of opportunistic infections seen in lentiviral infection.
authors.affiliation: Departments of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, 80523, USA.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Lehman
authors.forename: Kevin P
authors.initials: KP
authors.lastname: O'Halloran
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Fallon
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Habermann
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Campbell
authors.forename: Shila
authors.initials: S
authors.lastname: Nordone
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Dean
authors.forename: Edward A
authors.initials: EA
authors.lastname: Hoover
authors.forename: Paul R
authors.initials: PR
authors.lastname: Avery
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002415:Cats; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015870:Gene Expression; D016089:Immunodeficiency Virus, Feline; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12
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