Abstract
The condition of neutropenia, i.e., a reduced absolute neutrophil count in blood, constitutes a major risk factor for severe infections in the affected patients. Candida albicans and Candida glabrata are opportunistic pathogens and the most prevalent fungal species in the human microbiota. In immunocompromised patients, they can become pathogenic and cause infections with high mortality rates. In this study, we use a previously established approach that combines experiments and computational models to investigate the innate immune response during blood stream infections with the two fungal pathogens C. albicans and C. glabrata. First, we determine immune-reaction rates and migration parameters under healthy conditions. Based on these findings, we simulate virtual patients and investigate the impact of neutropenic conditions on the infection outcome with the respective pathogen. Furthermore, we perform in silico treatments of these virtual patients by simulating a medical treatment that enhances neutrophil activity in terms of phagocytosis and migration. We quantify the infection outcome by comparing the response to the two fungal pathogens relative to non-neutropenic individuals. The analysis reveals that these fungal infections in neutropenic patients can be successfully cleared by cytokine treatment of the remaining neutrophils; and that this treatment is more effective for C. glabrata than for C. albicans.
Highlights
The human immune system protects the body against various environmental cues, such as microorganisms
In case of C. glabrata, 81.0 ± 8.1% cells were associated with neutrophils, which is similar to C. albicans with 82.3 ± 7%
The association with monocytes is higher for C. glabrata with 10.1 ± 2.7%, while only 2.7 ± 1.9% C. albicans cells were associated with monocytes 4 h post infection
Summary
The human immune system protects the body against various environmental cues, such as microorganisms. It covers mechanisms on different levels ranging from physical barriers, like the skin and mucosal surfaces, down to cellular and molecular components of the innate and adaptive immune system [1]. Neutrophils constitute the highest fraction of blood leukocytes, as they make up over 70% of all blood leukocytes [2]. Since they can migrate to sites of infection and clear the organism from pathogens, they constitute an important part of the immune system.
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