Transcriptional Response in a Sepsis Mouse Model Reflects Transcriptional Response in Sepsis Patients.

Mortality due to sepsis remains unacceptably high, especially for septic shock patients. Murine models have been used to better understand pathophysiology mechanisms. However, the mouse model is still under debate. Herein we investigated the transcriptional response of mice injected with lipopolysaccharide (LPS) and compared it to either human cells stimulated in vitro with LPS or to the blood cells of septic patients. We identified a molecular signature composed of 2331 genes with an FDR median of 0%. This molecular signature is highly enriched in regulated genes in peritoneal macrophages stimulated with LPS. There is significant enrichment in several inflammatory signaling pathways, and in disease terms, such as pneumonia, sepsis, systemic inflammatory response syndrome, severe sepsis, an inflammatory disorder, immune suppression, and septic shock. A significant overlap between the genes upregulated in mouse and human cells stimulated with LPS has been demonstrated. Finally, genes upregulated in mouse cells stimulated with LPS are enriched in genes upregulated in human cells stimulated in vitro and in septic patients, who are at high risk of death. Our results support the hypothesis of common molecular and cellular mechanisms between mouse and human sepsis.

Use of Mpox Multiplex Serology in the Identification of Cases and Outbreak Investigations in the Democratic Republic of the Congo (DRC).

Human Mpox cases are increasingly reported in Africa, with the highest burden in the Democratic Republic of Congo (DRC). While case reporting on a clinical basis can overestimate infection rates, laboratory confirmation by PCR can underestimate them, especially on suboptimal samples like blood, commonly used in DRC. Here we used a Luminex-based assay to evaluate whether antibody testing can be complementary to confirm cases and to identify human transmission chains during outbreak investigations. We used left-over blood samples from 463 patients, collected during 174 outbreaks between 2013 and 2022, with corresponding Mpox and VZV PCR results. In total, 157 (33.9%) samples were orthopox-PCR positive and classified as Mpox+; 124 (26.8%) had antibodies to at least one of the three Mpox peptides. The proportion of antibody positive samples was significantly higher in Mpox positive samples (36.9%) versus negative (21.6%) (p < 0.001). By combining PCR and serology, 66 additional patients were identified, leading to an Mpox infection rate of 48.2% (223/463) versus 33.9% when only PCR positivity is considered. Mpox infections were as such identified in 14 additional health zones and 23 additional outbreaks (111/174 (63.8%) versus 88/174 (50.6%)). Our findings highlight the urgent need of rapid on-site diagnostics to circumvent Mpox spread.

Gene expression profiling in blood from cerebral malaria patients and mild malaria patients living in Senegal.

BACKGROUND: Plasmodium falciparum malaria remains a major health problem in Africa. The mechanisms of pathogenesis are not fully understood. Transcriptomic studies may provide new insights into molecular pathways involved in the severe form of the disease. METHODS: Blood transcriptional levels were assessed in patients with cerebral malaria, non-cerebral malaria, or mild malaria by using microarray technology to look for gene expression profiles associated with clinical status. Multi-way ANOVA was used to extract differentially expressed genes. Network and pathways analyses were used to detect enrichment for biological pathways. RESULTS: We identified a set of 443 genes that were differentially expressed in the three patient groups after applying a false discovery rate of 10%. Since the cerebral patients displayed a particular transcriptional pattern, we focused our analysis on the differences between cerebral malaria patients and mild malaria patients. We further found 842 differentially expressed genes after applying a false discovery rate of 10%. Unsupervised hierarchical clustering of cerebral malaria-informative genes led to clustering of the cerebral malaria patients. The support vector machine method allowed us to correctly classify five out of six cerebral malaria patients and six of six mild malaria patients. Furthermore, the products of the differentially expressed genes were mapped onto a human protein-protein network. This led to the identification of the proteins with the highest number of interactions, including GSK3B, RELA, and APP. The enrichment analysis of the gene functional annotation indicates that genes involved in immune signalling pathways play a role in the occurrence of cerebral malaria. These include BCR-, TCR-, TLR-, cytokine-, FcεRI-, and FCGR- signalling pathways and natural killer cell cytotoxicity pathways, which are involved in the activation of immune cells. In addition, our results revealed an enrichment of genes involved in Alzheimer's disease. CONCLUSIONS: In the present study, we examine a set of genes whose expression differed in cerebral malaria patients and mild malaria patients. Moreover, our results provide new insights into the potential effect of the dysregulation of gene expression in immune pathways. Host genetic variation may partly explain such alteration of gene expression. Further studies are required to investigate this in African populations.