Increased Expression of TLR3 in Lymph Nodes during Simian Immunodeficiency Virus Infection: Implications for Inflammation and Immunodeficiency

• Published in: Journal of Immunology Vol. 175; no. 8; pp. 5314 - 5323
• Main Authors: Sanghavi, Sonali K, Reinhart, Todd A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.10.2005
• Subjects: Animals; Cell Line; Gene Expression Regulation - immunology; Human immunodeficiency virus 1; Humans; Inflammation Mediators - metabolism; Inflammation Mediators - physiology; Interferon-alpha - physiology; Ligands; Lymph Nodes - immunology; Lymph Nodes - metabolism; Macaca mulatta; Polydeoxyribonucleotides - metabolism; RNA, Messenger - metabolism; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - metabolism; Simian immunodeficiency virus; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - metabolism; Spleen - cytology; Spleen - metabolism; Toll-Like Receptor 3 - biosynthesis; Toll-Like Receptor 3 - genetics; Toll-Like Receptor 9 - metabolism; Transcription, Genetic - physiology; Up-Regulation - physiology; Virus Replication - physiology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.175.8.5314

As pattern recognition receptors, TLRs signal and induce expression of multiple host defense genes including proinflammatory cytokines and chemokines. To investigate the mechanisms of up-regulation of proinflammatory cytokines and chemokines during SIV infection in rhesus macaques, we measured the relative levels of expression of TLRs 1-10 in lymphoid tissues during different stages of SIV infection. By real-time RT-PCR, TLR3 was determined to be up-regulated in macaque lymph nodes (LN) throughout the course of infection, whereas TLR9 was down-regulated during early stages of infection. CXCL9/Mig, CXCL10/IP-10, IFN-gamma, and IFN-alpha mRNAs were also increased during acute SIV infection and AIDS. Treatment of macaque spleen and LN cells with TLR3 and TLR9 ligands led to the induction of these same genes. TLR3 stimulation had disparate effects on viral transcription and viral replication, because poly(I:C), a model TLR3 ligand, stimulated the viral promoter but potently inhibited SIV replication in primary cultures of macaque spleen and LN cells. These findings identify roles for TLR3 inflammation in lymphoid tissues and in the immunopathogenesis of HIV-1/SIV, and suggest that TLR3 ligands could potentially be used to flush out latently infected cells that persist during antiretroviral therapies.