Conti et al. show that IL-17 is produced by tongue-resident populations of γδ T cells and nTh17 cells in response to oropharyngeal candidiasis in mice.

SUMMARY Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17raΔK13). Following oral Candida infection, Il17raΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra−/− mice. Susceptibility in Il17raΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3−/− mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3expression.

Lung DCs induce the expression of gut-homing molecules on T cells, resulting in their migration to the GI tract and protection against Salmonella infection after immunization

Protective immunity to protein vaccines is controlled by Flt3L-dependent classical LN-resident dendritic cells, and dampened by migratory dendritic cells.

Brain-computer interface (BCI) controlled prosthetic arms are being developed to restore function to people with upper-limb paralysis. This work provides an opportunity to analyze human cortical activity during complex tasks. Previously we observed that BCI control became more difficult during interactions with objects, although we did not quantify the neural origins of this phenomena. Here, we investigated how motor cortical activity changed in the presence of an object independently of the kinematics that were being generated using intracortical recordings from two people with tetraplegia. After identifying a population-wide increase in neural firing rates that corresponded with the hand being near an object, we developed an online scaling feature in the BCI system that operated without knowledge of the task. Online scaling increased the ability of two subjects to control the robotic arm when reaching to grasp and transport objects. This work suggests that neural representations of the environment, in this case the presence of an object, are strongly and consistently represented in motor cortex but can be accounted for to improve BCI performance.

Despite significant therapeutic advances for HIV-1 infected individuals, a preventative HIV-1 vaccine remains elusive. Studies focusing on early transmission events, including the observation that there is a profound loss of gastrointestinal (GI) CD4+ T cells during acute HIV-1 infection, highlight the importance of inducing HIV-specific immunity within the gut. Here, we report on the generation of cellular and humoral immune responses in the intestines by a mucosally administered, dendritic cell (DC) targeted vaccine. Our results show that nasally delivered α–CD205-p24 vaccine in combination with polyICLC, induced poly-functional immune responses within naso-pulmonary lymphoid sites that disseminated widely to systemic and mucosal (GI tract and the vaginal epithelium) sites. Qualitatively, while α–CD205-p24 prime-boost immunization generated CD4+ T cell responses, heterologous prime-boost immunization with α–CD205-p24 and NYVAC gag-p24 generated high levels of HIV-specific CD4+ and CD8+ T cells within the GI tract. Finally, DC targeting enhanced the amplitude and longevity of vaccine induced immune responses in the GI tract. This is the first report of a nasally delivered, DC targeted vaccine to generate HIV-specific immune responses in the GI tract and will potentially inform the design of preventative approaches against HIV-1 and other mucosal infections.

No abstract

This was an investigational device observational trial with the objective to evaluate the impact of distractions on intracortical brain-computer interface (BCI) performance. Two individuals with tetraplegia had microelectrode arrays implanted into their motor cortex for trials of intracortical BCI safety and performance. The primary task was moving a robotic arm between two targets as quickly as possible, performed alone and with various secondary distraction conditions. Primary outcomes included targets acquired, path efficiency, and subjective difficulty. There was no difference in the number of targets acquired for either subject with or without distractions. Median path efficiency was similar across all conditions (range: 0.766-0.846) except the motor distraction for Subject P2, where the median path efficiency dropped to 0.675 (p = 0.033, Mann-Whitney U test). Both subjects rated the overall difficulty of the task with and without distractions as low. Overall, intracortical BCI performance was robust to various distractions.