title: T cell responses are elicited against Respiratory Syncytial Virus in the absence of signalling through TLRs, RLRs and IL-1R/IL-18R.
abstract: Pattern recognition receptors (PRRs) and cytokine receptors are key players in the initiation of immune responses to infection. PRRs detecting viral RNA, such as toll like receptor (TLR)-3, -7/8, and RIG-I like receptors (RLRs; RIG-I and MDA-5), as well as cytokine receptors such as interleukin 1 receptor (IL-1R), have been implicated in responses to RNA viruses that infect the airways. The latter includes respiratory syncytial virus (RSV), a human pathogen that can cause severe lower respiratory tract infections, especially in infants. To evaluate the collective contribution of PRRs and IL-1R signalling to RSV immunity, we generated Myd88/Trif/Mavs(-/-) mice that are deficient in signalling by all TLRs, RLRs and IL-1R, as well as other cytokine receptors such as IL-18 receptor. Early production of pro-inflammatory mediators and lung infiltration by immune cells were completely abrogated in infected Myd88/Trif/Mavs(-/-) mice. However, RSV-specific CD8(+) T cells were elicited and recruited into the lungs and airways. Consistent with these findings, Myd88/Trif/Mavs(-/-) mice survived RSV infection but displayed higher viral load and weight loss. These data highlight an unappreciated level of redundancy in pathways that couple innate virus sensing to adaptive immunity, providing the host with remarkable resilience to infection.
authors.affiliation: Centre for Respiratory Infections, Respiratory Infections Section, St Mary's campus, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, W2 1PG, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Goritzka
authors.affiliation: Centre for Respiratory Infections, Respiratory Infections Section, St Mary's campus, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, W2 1PG, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Pereira
authors.affiliation: Centre for Respiratory Infections, Respiratory Infections Section, St Mary's campus, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, W2 1PG, UK.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Makris
authors.affiliation: Centre for Respiratory Infections, Respiratory Infections Section, St Mary's campus, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, W2 1PG, UK.
authors.forename: Lydia R
authors.initials: LR
authors.lastname: Durant
authors.affiliation: Centre for Respiratory Infections, Respiratory Infections Section, St Mary's campus, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, W2 1PG, UK.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Johansson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000818:Animals; D006801:Humans; D007239:Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology; D053574:Receptors, Interleukin-1 Type II / Q000235:genetics*; D053724:Receptors, Interleukin-18 / Q000235:genetics* / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000472:pathogenicity; D012141:Respiratory Tract Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019562:Viral Load
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D053594:Myeloid Differentiation Factor 88; D018121:Receptors, Cytokine; D053574:Receptors, Interleukin-1 Type II; D053724:Receptors, Interleukin-18; D051192:Receptors, Pattern Recognition; C508592:IL1R2 protein, human; C512612:MAVS protein, mouse; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse