Human dendritic cell interactions with the zoonotic parasite Cryptosporidium parvum result in activation and maturation.

Cryptosporidiosis in humans is caused by infection of the zoonotic apicomplexan parasite Cryptosporidium parvum. In 2006, it was included by the World Health Organization (WHO) in the group of the most neglected poverty-related diseases. It is characterized by enteritis accompanied by profuse catarrhalic diarrhea with high morbidity and mortality, especially in children of developing countries under the age of 5 years and in HIV patients. The vulnerability of HIV patients indicates that a robust adaptive immune response is required to successfully fight this parasite. Little is known, however, about the adaptive immune response against C. parvum. To have an insight into the early events of the adaptive immune response, we generated primary human dendritic cells (DCs) from monocytes of healthy blood donors and exposed them to C. parvum oocysts and sporozoites in vitro. DCs are equipped with numerous receptors that detect microbial molecules and alarm signals. If stimulation is strong enough, an essential maturation process turns DCs into unique activators of naïve T cells, a prerequisite of any adaptive immune response. Parasite exposure highly induced the production of the pro-inflammatory cytokines/chemokines interleukin (IL)-6 and IL-8 in DCs. Moreover, antigen-presenting molecules (HLA-DR and CD1a), maturation markers, and costimulatory molecules required for T-cell stimulation (CD83, CD40, and CD86) and adhesion molecules (CD11b and CD58) were all upregulated. In addition, parasite-exposed human DCs showed enhanced cell adherence, increased mobility, and a boosted but time-limited phagocytosis of C. parvum oocysts and sporozoites, representing other prerequisites for antigen presentation. Unlike several other microbial stimuli, C. parvum exposure rather led to increased oxidative consumption rates (OCRs) than extracellular acidification rates (ECARs) in DCs, indicating that different metabolic pathways were used to provide energy for DC activation. Taken together, C. parvum-exposed human DCs showed all hallmarks of successful maturation, enabling them to mount an effective adaptive immune response.

Influence of different pre-treatments on the resin infiltration depth into enamel of teeth affected by molar-incisor hypomineralization (MIH).

OBJECTIVES: This in vitro pilot study aimed to evaluate whether different pre-treatments (demineralization, deproteinization, (chemo-)mechanical reduction of the surface layer) influence the penetration depth of a resin infiltrant into MIH-affected enamel compared to initial carious lesions. METHODS: Thirty extracted human permanent molars with non-cavitated initial carious lesions (n = 5) or MIH (n = 25) were chosen and randomly assigned to six experimental groups: IC: initial caries; M: MIH; MN: MIH, 5.25% sodium hypochlorite; MM: MIH, microabrasion; MA: MIH, air abrasion; MAN: MIH, air abrasion and 5.25% sodium hypochlorite. A modified indirect dual fluorescence staining method was adopted to assess the penetration depth (PD) of the resin infiltrant and the lesion depth (LD) by confocal laser scanning microscopy (CLSM). Exemplarily, scanning electron microscopic (SEM) images were captured. The relationship between group assignment and penetration/lesion depth was estimated using a linear mixed model incorporating the tooth as random effect (two observations/tooth). The significance level was set at p < 0.05. RESULTS: For MIH-affected molars, the mean PD (in µm; median, [minimum-maximum]) were M (178.2 [32.5-748.9]), MN (275.6 [105.3-1131.0]), MM (48.7 [0.0-334.4]), MA (287.7 [239.4-491.7]), and MAN (245.4 [76.1-313.5]). Despite the observed differences in PD between the groups, these could not be statistically verified (Bonferroni, p = 0.322). The percentage penetration was significantly higher for IC than for MIH groups (Bonferroni, p < 0.05). SIGNIFICANCE: Compared to IC, resin infiltration into MIH-affected enamel ist more variable. Different pre-treatments influence the resin penetration into developmentally hypomineralized enamel to a fluctuating level.

Thermal Impact and the Relevance of Body Size and Activity on the Oxygen Consumption of a Terrestrial Snail, Theba pisana (Helicidae) at High Ambient Temperatures.

Metabolism, mainly driven by oxygen consumption, plays a key role in life, as it is one of the main ways to respond to extreme temperatures through internal processes. Theba pisana, a widespread Mediterranean land snail, is exposed to a wide range of ambient temperature. In this species the oxygen consumption was tested as a response variable by multiple regression modelling on the "explanatory" variables shell-free mass, temperature, and relative humidity. Our results show that the oxygen consumption of T. pisana can be well described (73.1%) by these three parameters. In the temperature range from 23 °C to 35 °C the oxygen consumption decreased with increasing temperature. Relative humidity, in the range of 67% to 100%, had the opposite effect: if it increases, oxygen consumption will increase as well. Metabolism is proportional to an individual's mass to the power of the allometric scaling exponent α, which is between 0.62 and 0.77 in the mentioned temperature range. CT scans of shells and gravimetry revealed the shell-free mass to be calculated by multiplying the shell diameter to the third power by 0.2105. Data were compared to metabolic scaling exponents for other snails reported in the literature.