Zakrzewska, A. | Search bioRxiv

bioRxiv2019

Diagnostic value of chest ultrasound in children with cystic fibrosis.

Cystic fibrosis (CF) is one of the most common genetic disorders in the Caucasian population. The disease has a progressive course and leads to reduced life quality and life expectancy. Standard diagnostic procedures used in the monitoring of CF patients, include methods exposing patients to the ionizing radiation. With increasing life expectancy in CF the cumulative dose of ionising radiation increases, prompting clinicians search for safer imaging studies. Despite its safety and availability lung ultrasound (LUS) is not routinely used in the diagnostic evaluation of CF patients.\n\nThe aim of the study was to evaluate the diagnostic value of LUS in children with CF compared to chest X-ray, and to assess the diagnostic value of the recently developed LUS score - CF-USS (Cystic Fibrosis Ultrasound Score).\n\nLUS was performed in 48 CF children aged from 5 to 18 years (24 girls and 24 boys). LUS consisted in the assessment of the pleura, lung sliding, A-line and B-line artifacts, \"lung rockets\", alveolar consolidations, air bronchogram and pleural effusion. Chest radiography was performed in all patients and analyzed according to the modified Chrispin-Norman score. LUS was analyzed according to CF-USS.\n\nCorrelation between the CF-USS and the modified Chrispin-Norman scores were moderate (R=0.52, p=0.0002) and strong in control studies. In 75% of patients undergoing LUS, small areas of subpleural consolidations were observed, not visible on X-rays. At the same time, LUS was not sensitive enough to visualize bronchial pathology, which plays an important role in assessing the disease progression.\n\nConclusionsLUS constitutes an invaluable tool for the diagnosis of subpleural consolidations. CF-USS results correlate with conventional x-ray modified Chrispin-Norman score. LUS should be considered an accessory radiographic examination in the monitoring of CF patients, and CF-USS may provide clinicians with valuable information concerning the disease progression.

scientific communication and education↗

bioRxiv2019

RNAseq profiling of leukocyte populations in zebrafish larvae reveals a cxcl11 chemokine gene as a marker of macrophage polarization during mycobacterial infection.

Macrophages are phagocytic cells from the innate immune system, which forms the first line of host defense against invading pathogens. These highly dynamic immune cells can adopt specific functional phenotypes, with the pro-inflammatory M1 and anti-inflammatory M2 polarization states as the two extremes. Recently, the process of macrophage polarization during inflammation has been visualized by real time imaging in larvae of the zebrafish. This model organism has also become widely used to study macrophage responses to microbial pathogens. To support the increasing use of zebrafish in macrophage biology, we set out to determine the complete transcriptome of zebrafish larval macrophages. We studied the specificity of the macrophage signature compared with other larval immune cells and the macrophage-specific expression changes upon infection. We made use of the well-established mpeg1, mpx, and lck fluorescent reporter lines to sort and sequence the transcriptome of larval macrophages, neutrophils, and lymphoid progenitor cells, respectively. Our results provide a complete dataset of genes expressed in these different immune cell types and highlight their similarities and differences. Major differences between the macrophage and neutrophil signatures were found within the families of proteinases. Furthermore, expression of genes involved in antigen presentation and processing was specifically detected in macrophages, while lymphoid progenitors showed expression of genes involved in macrophage activation. Comparison with datasets of in vitro polarized human macrophages revealed that zebrafish macrophages express a strongly homologous gene set, comprising both M1 and M2 markers. Furthermore, transcriptome analysis of low numbers of macrophages infected by the intracellular pathogen Mycobacterium marinum revealed that infected macrophages change their transcriptomic response by downregulation of M2-associated genes and overexpression of specific M1-associated genes. Among the infection-induced genes, a homolog of the human CXCL11 chemokine gene, cxcl11aa, stood out as the most strongly overexpressed M1 marker. Upregulation of cxcl11aa in Mycobacterium-infected macrophages was found to require the function of Myd88, a critical adaptor molecule in the Toll-like and interleukin 1 receptor pathways that are central to pathogen recognition and activation of the innate immune response. Altogether, our data provide a valuable data mining resource to support infection and inflammation research in the zebrafish model.

immunology↗