Pathogen recognition receptor crosstalk in respiratory syncytial virus sensing: a host and cell type perspective

Abstract

Human respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in young children, immunocompromised adults, and the elderly. The innate immune response plays a pivotal role in host defense against RSV, but whether severe outcomes following RSV infection result from excessive or poor innate immune recognition remains unclear. Recent research suggests a situation in which crosstalk between families of pattern recognition receptors (PRRs) occurs in a cell type-dependent manner. The current challenge to empower novel therapeutic approaches and vaccine development is to confirm the role of the individual receptors in RSV pathogenesis in humans.

Keywords: innate immunity; pathogen recognition receptors; pathogenesis; respiratory syncytial virus.

Figure 1

PRRs implicated in RSV sensing. The families of PRRs include TLRs: Toll-like receptors, RLRs: RIG-I-like receptors, NLRs: NOD-like receptors and dsRNA-BP: double-stranded RNA binding protein. The specific adaptors used by PRRs, including Myd88, TRIF and MAVS are indicated. Abbreviations: RD, regulatory domain; Hel, helicase domain; CD, CARD domain; Pro, proline-rich domain; TM, transmembrane domain; LRR, leucin-rich repeat; NBD, nucleotide binding domain; KD, kinase domain; RB, dsRNA binding domain.

Figure 2

Mechanisms of PRR activation during RSV replication cycle. RSV entry and replication cycle are described. A. Potential RSV-derived ligands for activation of cytosolic PRRs. B. Potential mechanisms of activation of endosomal TLRs. Solid lines depict the RSV replication cycle. Dashed lines and question marks indicate potential pathways and ligand PRRs interactions that need further investigation. Abbreviations: DI, defective interfering; DAMPs, damage-associated molecular patterns.