Browsing by Subject "Suppression"

Recent studies have linked expressive suppression to impairments in interpersonal functioning, but the mechanism underlying this relationship has not been well articulated. One possibility is that the individual who engages in expressive suppression is impaired in perceiving the emotions of others, a critical ability in successful interpersonal functioning. In the current study, participants were presented with a series of photographs of facial expressions that were manipulated so that they appeared to "morph" from neutral into full emotion expressions. As they viewed these images, participants were instructed to identify the expression as quickly as possible, by selecting one of the six emotion labels (happiness, sadness, fear, anger, surprise, and disgust) on the screen. Prior to this task, participants were randomized to one of three groups: instructed to mimic the expressions on the screen, instructed to suppress all emotion expressions, or not given specific instructions on how to control expressions (the control group). The speed with which participants accurately identified emotional expressions (emotion sensitivity) was the primary variable of interest. Overall, participants in the suppression condition were found to be slower to accurately identify emotions, while no statistically-significant differences were found between the mimicry and no-instructions conditions. The decreased emotion sensitivity in the suppression group could not be accounted for by impulsive responding, decreased sensitivity at full expression, or perceived difficulty of task.

Mast cells (MCs) are increasingly recognized as powerful sentinel cells responsible for modulating the early immune responses to a wide range of infectious agents. This protective role is attributable in part to their preponderance at the host-environment interface and their innate capacity to rapidly release modulators of immune cell trafficking which promotes the early recruitment of pathogen-clearing immune cells from the blood. However, host-adapted pathogens had been a critical threat to human for a long time because they have evolved mechanisms directed at overcoming protective immunity.

In this work, we outline Salmonella enterica serovar Typhimurium has evolved a novel mechanism to inactivate peripheral MCs resulting in limited neutrophil responses at infection sites in early stage of infection. Because of the delay in bacterial clearance at the point of entry, Salmonella are able to multiply and rapidly disseminate to distal sites. Suppression of local MCs' degranulation restricted outflow of vascular contents into infection sites, thus facilitating bacterial spread.

We discover MC suppression is mediated by the Salmonella Protein Tyrosine Phosphatase (SptP), which shares structural homology with Yersinia YopH. Interestingly, SptP, not only shares homology with phosphatases found in MCs, they are also homologous to YopH an effector protein expressed by plague causing Yersinia pestis. We show that YopH had MC suppressing abilities as SptP suggesting that this activity is shared among some of the more virulent bacterial pathogens. The functionally relevant domain in SptP is its enzymatic site and that it works by dephosphorylating the vesicle fusion protein N-ethylmalemide-sensitive factor (NSF) and by blocking phosphorylation of Syk, which is located in downstream and upstream of tyrosine phosphorylation signaling pathway in MCs.

Without SptP, orally challenged S. Typhimurium failed to suppress MC degranulation and exhibited limited colonization of the mesenteric lymph nodes. Administration of SptP to sites of Escherichia coli infection markedly enhanced its virulence. Thus, SptP-mediated inactivation of local MCs is a powerful mechanism utilized by S. Typhimurium to impede early innate immunity. This finding provides a logical explanation for why previous attempts by others to demonstrate a protective role for MCs against Salmonella infections have resulted in equivocal results.

Taken together, this work highlights an overlooked virulence mechanism possessed by certain host adapted pathogens to avoid the host's innate immune system. Additionally, this innate immune-quelling property of SptP may hold future promise in tempering harmful inflammatory disorders in the body of an immune competent host.