![]() ![]() Our model predicts that lung epithelial cells play an important role in fungal clearance and contribute to pro-inflammatory signaling by cytokine release upon conidial stimulation. fumigatus in a quantitative and time-resolved manner. In the presented study, we used the mathematical approach of dynamic optimization to understand the roles of human cells and virulence factors of A. The innate immune response against conidia in the lung alveoli is a highly dynamic process and involves the interplay of immune cells like macrophages and neutrophils as well as lung epithelial cells. Aspergillus fumigatus is a ubiquitous mold as well as potent pathogen causing life-threatening infections, invasive aspergillosis, via lung inhalation of fungal spores (conidia). In those patients the innate immune response is not able to efficiently clear fungal cells from body surfaces and stop an invasive growth into tissues and bloodstream infections. We expect that our model will contribute to improvement of treatment protocols by focusing on the critical components of immune response to fungi but also fungal virulence traits.įungal infections are an increasing problem and threat for individuals which suffer from an impairment of immune functions due to immunosuppressive therapies or diseases. Further, our model affirms the importance of neutrophils in invasive aspergillosis and underlines that the role of macrophages remains elusive. ![]() Both predictions were confirmed by in vitro experiments on established cell lines as well as primary lung cells. On the host side, we found that epithelial cells, which have been underappreciated, play a role in fungal clearance and are potent mediators of cytokine release. On the pathogen side, we predict in silico and confirm in vitro that germination speed is an important virulence trait of fungal pathogens due to the vulnerability of conidia against host defense. Using this model, we obtain key insights into major determinants of infection outcome on host and pathogen side. fumigatus conidia, we use dynamic optimization to obtain insight into the recruitment and depletion of alveolar macrophages and neutrophils. Since infection is a race between the innate immune system and the outgrowth of A. The resulting invasive aspergillosis is associated with devastating mortality rates. ![]() In immunocompromised individuals, conidia can grow out as hyphae that damage lung epithelium. Aspergillus fumigatus is an important human fungal pathogen and its conidia are constantly inhaled by humans. ![]()
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