Respiratory syncytial virus (RSV) infection isimmunological synapse ͉ virus evasion ͉ virulence mechanism ͉ adaptive immunity R espiratory syncytial virus (RSV) is the worldwide leading cause of infant hospitalization related to airway diseases. RSV infects Ͼ70% of children in the first year of life and by age 2, almost 100% of children have been infected at least once with this virus (1, 2). In addition, RSV reinfection is extremely frequent, suggesting that naturally acquired adaptive immunity to RSV is either inefficient or transient (2-4). It is thought that clearance of RSV would require the induction of a balanced Th1/Th2 adaptive immune response capable of inducing the production of neutralizing antibodies and IFN-␥-secreting cytotoxic CD8 ϩ T cells (CTLs) (5, 6). However, RSV-specific T cell responses generally fail to efficiently clear infection (7-9). Although functional RSV-specific memory CTLs and helper T cells can be observed in the blood and spleens of infected hosts, these cells show impaired effector function in infected lung tissues (10)(11)(12)(13)(14).Dendritic cells (DCs) are ubiquitous professional antigenpresenting cells (APCs) found in lymphoid and nonlymphoid tissues, where they locate strategically to capture antigens and present them to T cells as peptides bound to either MHC class I or II molecules (15, 16). These features render DCs as key components for the initiation and modulation of T cell immunity against pathogens, such as virus. Thus, several virulent microorganisms have developed molecular mechanisms to impair DC function and prevent clearance by adaptive immunity (17-21). RSV infection causes a significant increase in the number of mature DCs in mouse lungs (22,23) and has the capacity to infect and replicate within these cells (24-27), rendering them inefficient at inducing proliferation and IFN-␥ secretion by antigenspecific T cells (24,25). Inhibition of T cell activation by RSV has been suggested to be mediated by soluble molecules secreted by RSV-infected DCs, which reduce their capacity to induce IFN-␥ secretion by T cells (28). Although recent data indicate that RSV-induced secretion of IFN-and -␣ by human DCs can impair T cell activation (29), this phenomenon could also be observed upon T cell culture with RSV particles or cells expressing RSV antigens on their surface (30, 31). However, whether RSV-mediated inhibition applies to cognate pMHC recognition by T cells and the mechanism responsible for this inhibition remain unknown.Here, we have approached these questions by evaluating the effect of RSV infection on the capacity of murine DCs to activate T cells. We observed that DCs are efficiently infected by RSV and, although these cells mature upon infection, they are rendered unable to promote T cell activation in response to cognate-, allo-, and superantigen stimuli. Upon exposure to RSV-infected DCs, T cell proliferation and IL-2 secretion were significantly impaired, and T cells became unresponsive to subsequent stimulation with anti-CD3. Inhibition was not medi...

Respiratory syncytial virus (RSV) is

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SummarySalmonella enterica serovar Typhimurium can enter non-phagocytic cells, such as intestinal epithelial cells, by virtue of a Type Three Secretion System (TTSS) encoded in the Salmonella Pathogenicity Island 1 (SPI-1), which translocates bacterial effector molecules into the host cell. Salmonella can also be taken up by dendritic cells (DCs). Although the role of SPI-1 in non-phagocytic cell invasion is well established, its contribution to invasion of phagocytic cells has not been evaluated. Here, we have tested the invasive capacity of a S. Typhimurium strain lacking a key component of its TTSS-1 (DInvC) leading to defective translocation of SPI-1-encoded effectors. Whereas this mutant Salmonella strain was impaired for invasion of non-phagocytic cells, it was taken up by DCs at a significantly higher rate than wild-type Salmonella. Similar to wild-type Salmonella, the DInvC mutant strain retained the capacity to avoid antigen presentation to T cells. However, mice infected with the DInvC mutant strain showed higher survival rate and reduced organ colonization. Our data suggest that, besides promoting phagocytosis by non-phagocytic cells, SPI-1 modulates the number of bacteria that enters DCs. The SPI-1 could be considered not only as an inducer of epithelial cell invasion but as a controller of DC entry.