Iron overload is associated with increased susceptibility to pulmonary Pythium insidiosum infection in mice

Background Pythium insidiosum is a fungus-like oomycete capable of causing disease with high mortality rates. Although pulmonary Pythium insidiosum infections are rare, they are associated with an extremely high fatality rate. The mechanisms underlying Pythium insidiosum infection remain unclear and may be associated with immune dysregulation or iron overload. Existing animal models do not adequately replicate the pathophysiological process of pulmonary invasive infection by Pythium insidiosum in humans. Therefore, this study aims to establish a murine model of pulmonary Pythium insidiosum infection and to investigate the role of the Th1/Th2 immune balance in the progression of pulmonary infection. Methods BALB/c mice were divided into the following groups: control group, iron dextran (ID) group, cyclophosphamide (CTX) group, lipopolysaccharide (LPS) group, and groups affected by various factor combinations (e.g., LPS + CTX group, ID + CTX group, ID + LPS group). Mice were inoculated intratracheally with Pythium insidiosum hyphae after pretreatment. Body weight, clinical symptoms, inflammatory cell counts in venous blood and bronchoalveolar lavage fluid (BALF), pulmonary histopathological damage, pathogen burden, as well as serum levels of ferritin (FER), Th1 cytokines (IL-2, IL-12p70, IFN-γ, TNF-α) and Th2 cytokines (IL-4, IL-5, IL-13, IL-10) were assessed in each group. Results Among all groups, LPS + CTX and ID + CTX groups exhibited severe infection symptoms, significant weight loss, and the highest clinical symptom scores (all P 0.05), more consistent with a relative Th2 shift resulting from Th1 suppression. Conclusion This study established a murine model of pulmonary Pythium insidiosum infection for the first time through intratracheal hyphae inoculation following ID + CTX preconditioning. The findings suggest that iron overload is associated with Th1 immune response suppression and relative Th2 shift, which may be related to increased susceptibility and pathological damage in pulmonary Pythium insidiosum infection. However, further functional experiments are needed to validate causal relationships.