Infection vs. Reinfection: The Immunomodulation of Erythropoiesis.

Severe malarial anemia (SMA) increases the morbidity and mortality of Plasmodium, the causative agent of malaria. SMA is mainly developed by children and pregnant women in response to the infection. It is characterized by ineffective erythropoiesis caused by impaired erythropoietin (EPO) signaling. To gain new insights into the pathogenesis of SMA, we investigated the relationship between the immune system and erythropoiesis, conducting comparative analyses in a mouse model of malaria. Red blood cell (RBC) production was evaluated in infected and reinfected animals to mimic endemic occurrences. Higher levels of circulating EPO were observed in response to (re)infection. Despite no major differences in bone marrow erythropoiesis, compensatory mechanisms of splenic RBC production were significantly reduced in reinfected mice. Concomitantly, a pronounced immune response activation was observed in erythropoietic organs of reinfected animals in relation to single-infected mice. Aged mice were also used to mimic the occurrence of malaria in the elderly. The increase in symptom severity was correlated with the enhanced activation of the immune system, which significantly impaired erythropoiesis. Immunocompromised mice further support the existence of an immune-shaping regulation of RBC production. Overall, our data reveal the strict correlation between erythropoiesis and immune cells, which ultimately dictates the severity of SMA.

Pro-Inflammatory Priming of the Brain: The Underlying Cause of Parkinson's Disease.

Parkinson's disease (PD) is a multifactorial neurodegenerative pathology characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the brain. Aging is considered the main risk factor for the development of idiopathic PD. However, immunity and inflammation play a crucial role in the pathogenesis of this disorder. In mice, we showed that pro-inflammatory priming of the brain sensitizes to severe PD development, regardless of animal age. Age-related sub-acute inflammation, as well as the activation of the immune response upon exposure to harmful stimuli, enhances PD manifestations. The severity of PD is influenced by the engagement of host resistance mechanisms against infection based on the removal of iron (Fe) from the circulation. The sequestration of Fe by immune cells prevents pathogens from proliferating. However, it leads to the formation of a Fe-loaded circulating compartment. When entering the brain through a compromised blood-brain barrier, Fe-loaded immune cells contribute to enhancing neuroinflammation and brain Fe overload. Thus, pro-inflammatory priming of the brain exacerbates neuronal damage and represents a risk factor for the development of severe PD symptoms. Further investigations are now required to better understand whether therapeutic interventions inhibiting this phenomenon might protect against PD.

Evaluation of comparative scenarios from different sites of chestnut production using life cycle assessment (LCA): Case study in the Beira Interior region of Portugal.

The evaluation of the environmental impacts of chestnut production in the Beira Interior region (Portugal) is accessed. The comparative life cycle assessment (LCA) was performed with the use of openLCA software with 16 Environmental Footprint (EF) impact categories retrieved from the AGRIBALYSE database. The system boundary was from "cradle-to-farm gate" and the functional unit was 1 ton of chestnut delivered to consumers (only wholesale buyers). The processes model for the production of agricultural machinery, pesticides, fertilizers, and materials was modeled based on surveys and existing literature. The data was gathered from four different production areas: Serra da Estrela, Malcata, Gardunha, and Plateau area. Each site has two selected representative producers inner 250 km2 square radius environment. The results showed that the average GHG emissions in the low-input group (Estrela and Gardunha) were 1.83 kg CO2-eq/ton with the energy burden (80-89%) as main contribution emissions and in the intensive-input group (Malcata and Plateau) were 2.61 kg CO2-eq/ton with the main contribution source of emissions are fertilizer (76-83%). Sensitivity analysis results indicate shift input material and cultivation activities in chestnut production systems can be possible for all study areas without reducing yield production. The suggestions in this article can be used by farmers, policymakers, and other stakeholders to adopt new alternative production scenarios.

Interleukin-10 induces interferon-γ-dependent emergency myelopoiesis.

In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production are observed and often mediated by the pro-inflammatory cytokine interferon gamma (IFN-γ). Interleukin-10 (IL-10) inhibits IFN-γ secretion, but paradoxically, its therapeutic administration to humans causes hematologic changes similar to those observed in EM. In this work, we use different in vivo systems, including a humanized immune system mouse model, to show that IL-10 triggers EM, with a significant expansion of the myeloid progenitor compartment and production of myeloid cells. Hematopoietic progenitors display a prominent IFN-γ transcriptional signature, and we show that IFN-γ mediates IL-10-driven EM. We also find that IL-10, unexpectedly, reprograms CD4 and CD8 T cells toward an activation state that includes IFN-γ production by these T cell subsets in vivo. Therefore, in addition to its established anti-inflammatory properties, IL-10 can induce IFN-γ production and EM, opening additional perspectives for the design of IL-10-based immunotherapies.

Phonological characteristics of European and Brazilian Portuguese in children with Speech Sound Disorders.

This study aims to describe and compare the phonological characteristics of European Portuguese and Brazilian Portuguese preschool and school age children with Speech Sound Disorders (SSD). Speech samples for the European Portuguese Group (EPG) (n = 13) were collected using Subteste Fonético e Fonológico of Teste Fonético e Fonológico Avaliação da Linguagem Pré-Escolar. For the Brazilian Portuguese Group (BPG) (n = 13) Prova de Nomeação de Fonologia of Teste de Linguagem Infantil ABFW was applied. Different phonological measures were considered. Groups were matched according to sex, age, and percentage of correct consonants (revised). EPG presented more weak syllable deletion (p = .00); absolute index and relative index had a higher number of omissions (p = .003). BPG had more substitutions (p = .004). Intragroup analysis showed differences between groups in the occurrence of phonological processes (p ≤ 0.00). The most occurring was gliding of liquids, cluster reduction and devoicing in both groups; for the absolute index and relative index, the EPG presented differences in omission (p = .003), and the BPG in substitution (p = .002). Results suggested differences between groups in phonological processes occurrence and a relation with the most frequent type of error. These findings may occur due to the variation of phonetic and phonological characteristics between European Portuguese and Brazilian Portuguese in the two phonological tests. Linguistic variations had not directly influenced the measures studied, which characterized SSD. European Portuguese and Brazilian Portuguese children with SSD demonstrated similar characteristics as to the type of errors and phonological processes.

The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis.

Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10), described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection.

Tolerogenic insulin peptide therapy precipitates type 1 diabetes.

Daniel et al. (https://doi.org/10.1084/jem.20110574) have previously published in JEM a study on the preventive effect of tolerogenic vaccination with a strong agonist insulin mimetope in type 1 diabetes. Our study now challenges these results and shows that osmotic pump delivery of the modified insulin peptide R22E did not prevent hyperglycemia, accelerated disease onset, increased its incidence, and worsened insulitis.