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Critical Reviews™ in Immunology
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ISSN Imprimir: 1040-8401
ISSN En Línea: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v29.i6.40
pages 531-550

The Role of Toll-like Receptors in Regulating the Immune Response against Respiratory Syncytial Virus

Peter Klein Klouwenberg
Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
Lydia Tan
Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
Wendy Werkman
Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
Grada M. van Bleek
Department of Pediatrics, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
Frank Coenjaerts
University Medical Center Utrecht

SINOPSIS

Toll-like receptors (TLRs) play a distinct role in battling respiratory syncytial virus (RSV) infections. However, due to a lack of representative animal models and several early controversies, the field is unclear. In this systematic review, we have elucidated conflicting results and outlined important factors that might affect study outcomes. We reviewed studies that used different doses/viral strains, performed virus propagation in different cell lines, or used different mice strains. The following firm conclusions can be drawn: multiple TLRs activate innate immunity upon RSV infection; TLR4 can influence TLR2 expression, suggesting that optimal induction of multiple signaling pathways is required to elicit protective, rather than deleterious innate immune responses following infection; in mice, TLR4, TLR2/-6, and TLR7 have immune-stimulating properties, while TLR3 activation occurs later and appears to downregulate immune responses; in humans, polymorphism studies have demonstrated an important role for TLR4-signaling; and activation of TLR-signaling leads to antiviral cytokine production, such as TNF-a and IFNs. Viral factors may block these pathways, thereby contributing to immune evasion and RSV survival. A better understanding of the complex interplay between TLRs and severe RSV infections might lead to efficient prophylactic and therapeutic treatments, as well as the development of adequate vaccines combined with TLR adjuvants.


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