PMID- 27882497 OWN - NLM STAT- MEDLINE DCOM- 20180206 LR - 20181113 IS - 1538-2443 (Electronic) IS - 1355-0284 (Linking) VI - 23 IP - 2 DP - 2017 Apr TI - Soluble TLR2 and 4 concentrations in cerebrospinal fluid in HIV/SIV-related neuropathological conditions. PG - 250-259 LID - 10.1007/s13365-016-0495-7 [doi] AB - HIV in the central nervous system (CNS) mainly infects microglial cells which are known to express toll-like receptors (TLRs). This paper aimed to study the role of soluble TLR2 (sTLR2), sTLR4, and other inflammatory markers in cerebrospinal fluid (CSF) in HIV/Simian immunodeficiency virus (SIV)-related neurological sequelae. We determined sTLR2 and sTLR4 levels in CSF and serum/plasma of SIV-infected rhesus macaques with and without neurological sequelae, as well as in HIV-infected patients with and without cognitive impairments and Alzheimer's disease (AD) patients and matched controls. CSF cytokines and chemokines levels were analyzed in macaques as markers of neuroinflammation, while neopterin and S100B CSF concentrations were measured in HIV-infected patients as microglial and astrocyte marker, respectively. We found detectable levels of sTLR2 and sTLR4 in CSF of macaques and humans. Furthermore, CSF sTLR2 and sTLR4 concentrations were higher in SIV-infected macaques with neurological sequelae compared to those without neurological complications (p = 0.0003 and p = 0.0006, respectively). CSF IL-8 and monocyte chemoattractant protein-1 (MCP-1) levels were elevated in macaques with neurological sequelae, and a positive correlation was found between CSF levels of sTLR2/4 and IL-8 and MCP-1. Also in humans, elevated CSF sTLR4 levels were found in HIV-infected patients with cognitive impairments compared to HIV-infected patients with normal cognition (p = 0.019). Unlike CSF S100B levels, neopterin correlated positively with sTLR2 and sTLR4. No difference was found in plasma and CSF sTLR2 and sTLR4 levels between AD patients and control subjects (p = 0.26). In conclusion, CSF sTLR2 and sTLR4 may play a role in HIV/SIV-related neuroinflammation and subsequent neuropathology. FAU - Mothapo, Khutso M AU - Mothapo KM AD - Department of Internal Medicine and Nijmegen Institute for Health Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. kmothapo@gmail.com. FAU - Ten Oever, J AU - Ten Oever J AD - Department of Internal Medicine and Nijmegen Institute for Health Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. FAU - Koopmans, P AU - Koopmans P AD - Department of Internal Medicine and Nijmegen Institute for Health Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. FAU - Stelma, F F AU - Stelma FF AD - Department of Medical Microbiology-Section Virology, Radboud University Medical Center, Nijmegen, The Netherlands. FAU - Burm, S AU - Burm S AD - Alternatives Unit, Biomedical Primate Research Centre, Rijswijk, The Netherlands. FAU - Bajramovic, J AU - Bajramovic J AD - Alternatives Unit, Biomedical Primate Research Centre, Rijswijk, The Netherlands. FAU - Verbeek, M M AU - Verbeek MM AD - Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. FAU - Rikkert, M G Olde AU - Rikkert MGO AD - Radboudumc Alzheimer Centre, Department of Geriatric Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. FAU - Netea, M G AU - Netea MG AD - Department of Internal Medicine and Nijmegen Institute for Health Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. FAU - Koopman, G AU - Koopman G AD - Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands. FAU - van der Ven, A J AU - van der Ven AJ AD - Department of Internal Medicine and Nijmegen Institute for Health Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161123 PL - United States TA - J Neurovirol JT - Journal of neurovirology JID - 9508123 RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-8) RN - 0 (S100 Calcium Binding Protein beta Subunit) RN - 0 (S100B protein, human) RN - 0 (TLR2 protein, human) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 670-65-5 (Neopterin) SB - IM MH - Adult MH - Alzheimer Disease/blood/*cerebrospinal fluid/complications/virology MH - Animals MH - Astrocytes/immunology/pathology/virology MH - Biomarkers/blood/cerebrospinal fluid MH - Case-Control Studies MH - Chemokine CCL2/cerebrospinal fluid/genetics/immunology MH - Cognitive Dysfunction/blood/*cerebrospinal fluid/complications/virology MH - Female MH - Gene Expression MH - HIV/immunology/pathogenicity MH - HIV Infections/blood/*cerebrospinal fluid/complications/virology MH - Humans MH - Interleukin-8/cerebrospinal fluid/genetics/immunology MH - Macaca mulatta MH - Male MH - Microglia/immunology/pathology/virology MH - Middle Aged MH - Neopterin/cerebrospinal fluid/genetics/immunology MH - S100 Calcium Binding Protein beta Subunit/cerebrospinal fluid/genetics/immunology MH - Simian Acquired Immunodeficiency Syndrome/blood/*cerebrospinal fluid/virology MH - Simian Immunodeficiency Virus/immunology/pathogenicity MH - Solubility MH - Toll-Like Receptor 2/genetics/*immunology MH - Toll-Like Receptor 4/genetics/*immunology OTO - NOTNLM OT - HAND OT - HIV neuroinflammation OT - Pro-inflammation OT - SIV neuroinflammation OT - sTLR2 OT - sTLR4 EDAT- 2016/11/25 06:00 MHDA- 2018/02/07 06:00 CRDT- 2016/11/25 06:00 PHST- 2016/08/11 00:00 [received] PHST- 2016/10/20 00:00 [accepted] PHST- 2016/10/18 00:00 [revised] PHST- 2016/11/25 06:00 [pubmed] PHST- 2018/02/07 06:00 [medline] PHST- 2016/11/25 06:00 [entrez] AID - 10.1007/s13365-016-0495-7 [pii] AID - 10.1007/s13365-016-0495-7 [doi] PST - ppublish SO - J Neurovirol. 2017 Apr;23(2):250-259. doi: 10.1007/s13365-016-0495-7. Epub 2016 Nov 23.