HIV-1 increases TLR responses in human primary astrocytes.

M Jesús Serramía,Susana Álvarez,M Ángeles Muñoz-Fernández

doi:10.1038/srep17887

M Jesús Serramía, Susana Álvarez + Show 1 more

Open Access

https://doi.org/10.1038/srep17887

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Abstract

Astrocytes are the major glial cell within the central nervous system and have a number of important physiological properties related to brain homeostasis. They provide trophic support to neurons and are immune cells with key roles during states-of-inflammation. The potential for production of proinflammatory cytokines and its consequences has been studied in the context of HIV-1 infection of normal human astrocytes (NHA). NHA express TLR3, TLR4, and TLR5. TLR3 ligation induced the strongest proinflammatory polarizing response, characterized by generation of high levels of TNF-α, IL-6, and IL-8. HIV-1 increased the transient production of key inflammatory mediators, and exposure to LPS of HIV-1-infected cells increased significantly the cytokine secretion. We confirmed that it is necessary viral gene expression from the moment of pretreatment with antiretrovirals inhibited totally HIV-1-induced TLR response. The higher response to LPS from HIV-1-infected cells did not correlate with TLR4 or MyD88 increased expression. LPS responsiveness of infected cells parallels MHC class II expression, but not CD14. HIV-1-infected NHA present increased sensitivity to the proinflammatory effects of LPS. If this phenomenon occurs in vivo, it will contribute to the immunopathogenesis of this disease and may ultimately offer novel targets for immunomodulatory therapy.

Highlights

Astrocytes are the major glial cell within the central nervous system and have a number of important physiological properties related to brain homeostasis
To characterize the expression of Toll-like receptors (TLR) 1-10 in normal human astrocytes, NHA cells, we examined the cells under basal conditions
NHA basally express mRNA for TLR3, TLR4, and TLR5 (Fig. 1a), whereas the expression of the rest of TLR was lack compared with the positive controls

Summary

Introduction

Astrocytes are the major glial cell within the central nervous system and have a number of important physiological properties related to brain homeostasis. The hallmarks of HIV-1 associated neuropathology include brain atrophy, white matter gliosis, and neuronal cell loss[1,2] This neurological damage, especially gliosis and inflammation has been found to correlate with increased production of proinflammatory cytokines and chemokines[3,4,5], and can be caused by viral proteins, inflammatory cytokines resulting from systemic infection that cross the blood-brain barrier (BBB) or by toxic factors secreted in the brain by virus-infected or activated cells (reviewed by[6]). Toll-like receptors (TLR) play pivotal roles in the recognition of pathogen-specific patterns and the subsequent initiation of innate and adaptive immune responses[9] It has been described several effects after TLR stimulation in brain cells, mainly in microglia[10,11]. Several prior studies have looked at TLR www.nature.com/scientificreports/

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