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HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status?

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Abstract

Pattern recognition receptors (PRRs) are involved in direct recognition of viruses, promoting cellular activation and the production of pro-inflammatory cytokines. However, despite the reduced systemic immune activation described in HIV-1-exposed seronegatives (HESNs), few studies have focused on determining the relationship between PRR expression and cytokine production. We have aimed here to evaluate the expression level of PRRs and cytokines in HESNs, HIV-1 patients and healthy donors. Basal PRR expression levels in PBMCs, dendritic cells (DCs) and monocytes, and plasma cytokine levels as well as the PRR ligand-induced cytokine productions were determined by flow cytometry, qPCR and ELISA. Higher TLR2/4 expression in DCs and monocytes from HESNs was observed. Nevertheless, TLR4/8, NOD2 and RIG-I mRNA levels were lower in PBMCs from HESNs than HIV-1-infected patients. Comparable IL-1β, IL-18 and TNF-α mRNA levels were observed among the groups examined; however, at the protein level, production of IL-1β, IL-6 and IL-10 was significantly lower in plasma from HESNs than from HIV-1-infected patients. Our results suggest that exposure to HIV-1 without infection could be associated with reduced basal pro-inflammatory responses. Further studies are required to define the cell subsets responsible for these differences and the role of PRRs on protection against HIV-1 infection.

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Acknowledgments

The authors thank the patients and control individuals who participated in this study and the collaboration of the personnel from the institutions where the patients were recruited. We acknowledge the help of Anne-Lise Haenni for critically reading and reviewing of the manuscript. The authors also acknowledge the technical assistance of Diana Giraldo, Lanie Ruiz and Maria Patricia García.

Author contributions

J.C.H. and S.U.I. were responsible for the conception and design of the project, as well as the acquisition, analysis and interpretation of the data. The authors read and approved the final manuscript.

Sources of financial

This study was funded by COLCIENCIAS, Grant No. 111549326099, and Universidad de Antioquia (estrategia de sostenibilidad, 2014–2015). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. INFETTARE, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia

    Juan C. Hernandez

  2. St Laurent Institute, 317 New Boston St, Woburn, MA, 01801, USA

    Georges St Laurent III

  3. Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA, Calle 70 No. 52-21, Medellín, Colombia

    Silvio Urcuqui-Inchima

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  1. Juan C. Hernandez
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  2. Georges St Laurent III
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HESNs express lower NOD2 mRNA levels than HIV-1-infected patients. The mRNA of several NOD-like receptors and RIG-I-like receptors was measured using qRT-PCR and normalized with the housekeeping genes β-actin, GAPDH and β2-microglobulin. Relative units of transcripts versus average of housekeeping gene transcripts are shown as median and range. Comparisons were made by the Kruskal–Wallis test and Dunn’s post-tests. The level of significance was p < 0.05 (*). Median with ranges is shown. Healthy donors (n = 13), HIV-1-infected patients (n = 31) and HESNs (n = 11) (PDF 46 kb)

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Hernandez, J.C., St Laurent, G. & Urcuqui-Inchima, S. HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status?. Immunol Res 64, 280–290 (2016). https://doi.org/10.1007/s12026-015-8748-8

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