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Evidence of Neutrophils and Neutrophil Extracellular Traps in Human NMSC with Regard to Clinical Risk Factors, Ulceration and CD8^+ T Cell Infiltrate
No full textNon-melanoma skin cancers (NMSC), including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC), are increasingly common and present significant healthcare challenges. Neutrophil extracellular traps (NETs), chromatin fibers expulsed by neutrophil granulocytes, can promote immunotherapy resistance via an impairment of CD8^+ T cell-mediated cytotoxicity. Here, to identify a potential therapeutic target, we investigate the expulsion of NETs and their relation to CD8^+ T cell infiltration in NMSC. Immunofluorescence staining for neutrophils (CD15) and NETs (H3cit), as well as immunohistochemistry for cytotoxic T cells (CD8^+) on human cSCCs (n = 24), BCCs (n = 17) and MCCs (n = 12), revealed a correlation between neutrophil infiltration and ulceration diameter in BCC and MCC, but not in cSCC. In BCC and cSCC, neutrophil infiltration also correlated with the cross-sectional area (CSA). NETs were not associated with established risk factors but with the presence of an ulceration, and, in cSCC, with abscess-like structures. CD8^+ T cell infiltration was not reduced in tumors that were NET-positive nor in those with a denser neutrophil infiltration. This study is the first to report and characterize NETs in NMSC. Thus, it gives an incentive for further research in this relevant yet understudied topic
Experimental evolution of a pathogen confronted with innate immune memory increases variation in virulence
No full textUnderstanding the drivers and mechanisms of virulence evolution is still a major goal of evolutionary biologists and epidemiologists. Theory predicts that the way virulence evolves depends on the balance between the benefits and costs it provides to pathogen fitness. Additionally, host responses to infections, such as resistance or tolerance, play a critical role in shaping virulence evolution. But, while the evolution of pathogens has been traditionally studied under the selection pressure of host adaptive immunity, less is known about their evolution when confronted to simpler and less effective forms of immunity such as immune priming. In this study, we used a well-established insect model for immune priming – red flour beetles and their bacterial pathogen Bacillus thuringiensis tenebrionis – to test how this form of innate immune memory drives the pathogen evolution. Through controlled experimental evolution of the pathogen in primed versus non-primed hosts, we found no change in average virulence after eight selection cycles in primed host. Nonetheless, we observed a notable rise in the variability of virulence, defined as the ability to kill hosts, among independent pathogen lines that evolved in primed hosts, and the bacteria were unable to develop resistance to host priming. Whole genome sequencing revealed increased activity in the bacterial mobilome (prophages and plasmids). Expression of the Cry toxin – a well-known virulence factor – was linked to evolved differences in copy number variation of the cry-carrying plasmid, though this did not correlate directly with virulence. These findings highlight that innate immune memory can drive variability in pathogen traits, which may favor adaptation to variable environments. This underscores the need to consider pathogen evolution in response to innate immune memory when applying these mechanisms in medicine, aquaculture, pest control, and insect mass production
Fingerprint Sweat Pore Density in Patients with Oligodontia: A Controlled Clinical Trial
No full textBackground/Objectives: There is a lack of evidence for the relationship between sweat pores and tooth agenesis. The aim of this study was to compare sweat pore density on fingertips between a group of patients with oligodontia and a control group without tooth agenesis. Methods: This parallel-group controlled clinical trial included 28 patients. Fourteen patients (f/m 9/5; mean age 13.5 ± 3.5 years) with ≥6 congenitally missing permanent teeth, excluding third molars (M3), were enrolled in the study group. The matched control group consisted of 14 patients (f/m 9/5; mean age 12.8 ± 1.8 years) without tooth agenesis. Impressions of 168 fingertips (left and right index, middle, and ring fingers) of the participating subjects were taken and examined using a scanning electron microscope with a 5.85 mm × 4.29 mm region of interest at the center of the fingertip. The primary outcome was the pore-to-pore distance (μm) on a dermal ridge, and the secondary outcome was the number of sweat pores per cm2, while pore numbers were adjusted for individual body surface area (BSA). Results: There were no statistically significant differences in age, height, weight, and BSA between the groups. The study group had 11.07 ± 4.03 missing teeth, excluding M3. There was a statistically significant difference (p = 0.006) in the distance between adjacent pores on a dermal ridge between the study and control groups (354.89 ±32.41 μm vs. 340.31 ±39.04 μm). The unadjusted pore numbers showed a statistically significant difference between the groups, but after adjustment for BSA, this difference was no longer present. Conclusions: Patients with oligodontia differed from subjects without tooth agenesis in the distance between two adjacent sweat pores on a dermal ridge. However, the differences were small and of limited clinical significance. Increased pore distance appears to be a better predictor of oligodontia/ectodermal dysplasia than pore number
Flexible use of post-saccadic visual feedback in oculomotor learning
No full textSaccadic eye movements bring objects of interest onto our fovea. These gaze shifts are essential for visual perception of our environment and the interaction with the objects within it. They precede our actions and are thus modulated by current goals. It is assumed that saccadic adaptation, a recalibration process that restores saccade accuracy in case of error, is mainly based on an implicit comparison of expected and actual post-saccadic position of the target on the retina. However, there is increasing evidence that task demands modulate saccade adaptation and that errors in task performance may be sufficient to induce changes to saccade amplitude. We investigated if human participants are able to flexibly use different information sources within the post-saccadic visual feedback in task-dependent fashion. Using intra-saccadic manipulation of the visual input, participants were either presented with congruent post-saccadic information, indicating the saccade target unambiguously, or incongruent post-saccadic information, creating conflict between two possible target objects. Using different task instructions, we found that participants were able to modify their saccade behavior such that they achieved the goal of the task. They succeeded in decreasing saccade gain or maintaining it, depending on what was necessary for the task, irrespective of whether the post-saccadic feedback was congruent or incongruent. It appears that action intentions prime task-relevant feature dimensions and thereby facilitated the selection of the relevant information within the post-saccadic image. Thus, participants use post-saccadic feedback flexibly, depending on their intentions and pending actions
