CD11c+CD8alpha+ dendritic cells promote protective immunity to respiratory infection with Bordetella pertussis.

CD11c(+)CD8alpha(+) and CD103(+) dendritic cells (DC) have been shown to promote regulatory T cell responses and mediate tolerance in the gastrointestinal tract. These cells have also been identified in the lung, but their role in immunity to respiratory tract infection is not clear. In this study, we have used a murine model of infection with Bordetella pertussis to examine the function of DC subtypes in protective immunity in the lungs. We found a dramatic increase in the numbers of CD11c(+)CD8alpha(+) DC in the cervical lymph nodes within 4 h of challenge with B. pertussis and these DC could acquire particulate Ag from the upper respiratory tract. CD11c(+)CD8alpha(+) DC also infiltrated the lung with a peak 7 days after B. pertussis challenge. The infiltrating CD11c(+)CD8alpha(+) DC expressed MHC, costimulatory and activation markers indicative of mature DC. The CD11c(+)CD8alpha(+) DC in the cervical lymph nodes expressed IL-4 and IL-10 and lower levels of IFN-gamma, but in the lungs expressed predominantly IFN-gamma. Depletion of CD8alpha(+) cells early in infection attenuated Th1 responses in the lungs and significantly reduced bacterial clearance. Conversely, transfer of FLT3 ligand (FL)-expanded CD11c(+)CD8alpha(+) DC enhanced bacterial clearance, whereas GM-CSF-expanded conventional DC had no effect. The numbers of CD11c(+)CD8alpha(+)CD103(+) cells were also increased during the early phase of infection. Blocking CD103 function caused a significant delay in bacterial clearance and a reduction in cellular infiltration into the lungs. These findings demonstrate that CD11c(+)CD8alpha(+) and CD11c(+)CD103(+)DC play a protective role in mediating immunity to B. pertussis infection in the respiratory tract.

Emotion and deliberative reasoning in moral judgment.

According to an influential dual-process model, a moral judgment is the outcome of a rapid, affect-laden process and a slower, deliberative process. If these outputs conflict, decision time is increased in order to resolve the conflict. Violations of deontological principles proscribing the use of personal force to inflict intentional harm are presumed to elicit negative affect which biases judgments early in the decision-making process. This model was tested in three experiments. Moral dilemmas were classified using (a) decision time and consensus as measures of system conflict and (b) the aforementioned deontological criteria. In Experiment 1, decision time was either unlimited or reduced. The dilemmas asked whether it was appropriate to take a morally questionable action to produce a "greater good" outcome. Limiting decision time reduced the proportion of utilitarian ("yes") decisions, but contrary to the model's predictions, (a) vignettes that involved more deontological violations logged faster decision times, and (b) violation of deontological principles was not predictive of decisional conflict profiles. Experiment 2 ruled out the possibility that time pressure simply makes people more like to say "no." Participants made a first decision under time constraints and a second decision under no time constraints. One group was asked whether it was appropriate to take the morally questionable action while a second group was asked whether it was appropriate to refuse to take the action. The results replicated that of Experiment 1 regardless of whether "yes" or "no" constituted a utilitarian decision. In Experiment 3, participants rated the pleasantness of positive visual stimuli prior to making a decision. Contrary to the model's predictions, the number of deontological decisions increased in the positive affect rating group compared to a group that engaged in a cognitive task or a control group that engaged in neither task. These results are consistent with the view that early moral judgments are influenced by affect. But they are inconsistent with the view that (a) violation of deontological principles are predictive of differences in early, affect-based judgment or that (b) engaging in tasks that are inconsistent with the negative emotional responses elicited by such violations diminishes their impact.