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Altered bone marrow dendritic cell cytokine production to toll‐like receptor and CD40 ligation during chronic feline immunodeficiency virus infection
Author(s) -
Lehman Tracy L.,
O’Halloran Kevin P.,
Fallon Samantha A.,
Habermann Lindsey M.,
Campbell Jennifer A.,
Nordone Shila,
Dean Gregg A.,
Hoover Edward A.,
Avery Paul R.
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02907.x
Subject(s) - feline immunodeficiency virus , immunology , cytokine , biology , cd40 , ligation , dendritic cell , bone marrow , toll like receptor , virology , immune system , virus , lentivirus , innate immune system , microbiology and biotechnology , cytotoxic t cell , viral disease , in vitro , biochemistry
Summary 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.

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