Circulating Nestin-GFP+ Cells Participate in the Pathogenesis of Paracoccidioides brasiliensis in the Lungs

Multiple infectious diseases lead to impaired lung function. Revealing the cellular mechanisms involved in this impairment is crucial for the understanding of how the lungs shift from a physiologic to a pathologic state in each specific condition. In this context, we explored the pathogenesis of Paracoccidioidomycosis, which affects pulmonary functioning. The presence of cells expressing Nestin-GFP has been reported in different tissues, and their roles as tissue-specific progenitors have been stablished in particular organs. Here, we explored how Nestin-GFP + cells are affected after lung infection by Paracoccidioides brasiliensis , a model of lung granulomatous inflammation with fibrotic outcome. We used Nestin-GFP transgenic mice, parabiosis surgery, confocal microscopy and flow cytometry to investigate the participation of Nestin-GFP + cells in Paracoccidioides brasiliensis pathogenesis. We revealed that these cells increase in the lungs post- Paracoccidioides brasiliensis infection, accumulating around granulomas. This increase was due mainly to Nestin-GPF + cells derived from the blood circulation, not associated to blood vessels, that co-express markers suggestive of hematopoietic cells (Sca-1, CD45 and CXCR4). Therefore, our findings suggest that circulating Nestin-GFP + cells participate in the Paracoccidioides brasiliensis pathogenesis in the lungs. Graphical abstract