Respiratory syncytial virus (RSV) is the major cause of respiratory illness in infants worldwide. Neurologic alterations, such as seizures and ataxia, have been associated with RSV infection. We demonstrate the presence of RSV proteins and RNA in zones of the brainsuch as the hippocampus, ventromedial hypothalamic nucleus, and brainstem-of infected mice. One month after disease resolution, rodents showed behavioral and cognitive impairment in marble burying (MB) and Morris water maze (MWM) tests. Our data indicate that the learning impairment caused by RSV is a result of a deficient induction of long-term potentiation in the hippocampus of infected animals. In addition, immunization with recombinant bacillus Calmette-Guérin (BCG) expressing RSV nucleoprotein prevented behavioral disorders, corroborating the specific effect of RSV infection over the central nervous system. Our findings provide evidence that RSV can spread from the airways to the central nervous system and cause functional alterations to the brain, both of which can be prevented by proper immunization against RSV.espiratory syncytial virus (RSV) is an enveloped virus with a negative-sensed, single-stranded RNA genome that encodes 11 proteins (1, 2). RSV is the most prevalent pathogen of the Paramyxoviridae family and is the leading cause of lower respiratory tract infection in infants worldwide. RSV infects more than 70% of children in the first year of life, and 100% of children by age 2 years (3, 4). Although most symptoms of RSV infection, such as bronchiolitis and pneumonia, are related to airway inflammation, several central nervous system (CNS) manifestations have been reported in ∼2% of patients with RSVassociated bronchiolitis (5), including seizures, central apnea, lethargy, feeding or swallowing difficulties, muscular tone or strabismus abnormalities, cerebrospinal fluid (CSF) abnormalities, and encephalopathy (6-8). Recently, there has been an increase in the number of case reports on RSV-caused encephalopathy, highlighting the importance of these symptoms (9).Previous clinical studies have suggested an association between neurological symptoms and RSV infection (6,8,10), and other studies have documented the presence of RSV and RSV-specific antibodies in the CSF of patients suffering from severe bronchiolitis (11, 12). However, the pathophysiological mechanism responsible for RSV-caused encephalopathy remains undefined.Despite evidence demonstrating the presence of RSV in the CSF of infected children and CNS alterations resulting from severe respiratory infection by this virus, several aspects of RSV biology regarding the CNS, such as the entrance mechanism, localization, and spreading of RSV in the CNS and its associated tissues, remain obscure. Here, we evaluated whether RSV was able to access the CNS and cause cognitive sequelae using BALB/c mice and Sprague-Dawley rats. Immunofluorescence and quantitative real-time RT-PCR assays revealed the presence of both RSV nucleoprotein (N) and genetic material in the brains of infected anima...

Highlights d P. aeruginosa-infected macrophages produce itaconate d Itaconate generates membrane stress in P. aeruginosa d Itaconate leads to decreased LPS, but increased EPS, to promote biofilm formation d The EPS-itaconate axis thwarts immune clearance enabling chronic infection

Human respiratory syncytial virus (hRSV) is the leading cause of bronchiolitis and pneumonia in young children worldwide. The recurrent hRSV outbreaks and reinfections are the cause of a significant public health burden and associate with an inefficient antiviral immunity, even after disease resolution. Although several mouse-and human cell-based studies have shown that hRSV infection prevents naïve T-cell activation by antigen-presenting cells, the mechanism underlying such inhibition remains unknown. Here, we show that the hRSV nucleoprotein (N) could be at least partially responsible for inhibiting T-cell activation during infection by this virus. Early after infection, the N protein was expressed on the surface of epithelial and dendritic cells, after interacting with trans-Golgi and lysosomal compartments. Further, experiments on supported lipid bilayers loaded with peptide-MHC (pMHC) complexes showed that surface-anchored N protein prevented immunological synapse assembly by naive CD4 + T cells and, to a lesser extent, by antigen-experienced T-cell blasts. Synapse assembly inhibition was in part due to reduced T-cell receptor (TCR) signaling and pMHC clustering at the T-cell− bilayer interface, suggesting that N protein interferes with pMHC− TCR interactions. Moreover, N protein colocalized with the TCR independently of pMHC, consistent with a possible interaction with TCR complex components. Based on these data, we conclude that hRSV N protein expression at the surface of infected cells inhibits T-cell activation. Our study defines this protein as a major virulence factor that contributes to impairing acquired immunity and enhances susceptibility to reinfection by hRSV.