Inflammatory and immunopathological differences in brains of permissive and non-permissive hosts with Angiostrongylus cantonensis infection can be identified using 18F/FDG/PET-imaging.

BACKGROUND: Angiostrongylus cantonensis is a parasite that mainly infects the heart and pulmonary arteries of rats and causes human eosinophilic meningitis or meningoencephalitis in certain geographical areas. Current diagnostic methods include detection of the parasite in cerebrospinal fluid (CSF) and eosinophilic immune examination after lumbar puncture, which may be risky and produce false-positive results. 18F- Fluorodeoxyglucose (FDG), a Positron emission tomography (PET) tracer, has been used to assess different pathological or inflammatory changes in the brains of patients. In this study, we hypothesized that A. cantonensis infection-induced inflammatory and immunomodulatory factors of eosinophils result in localized pathological changes in the brains of non-permissive hosts, which could be analyzed using in vivo 18F-FDG PET imaging. METHODOLOGY/FINDINGS: Non-permissive host ICR mice and permissive host SD rats were infected with A. cantonensis, and the effects of the resulting inflammation on 18F-FDG uptake were characterized using PET imaging. We also quantitatively measured the distributed uptake values of different brain regions to build an evaluated imaging model of localized neuropathological damage caused by eosinophilic inflammation. Our results showed that the uptake of 18F-FDG increased in the cerebellum, brainstem, and limbic system of mice at three weeks post-infection, whereas the uptake in the rat brain was not significant. Immunohistochemical staining and western blotting revealed that Iba-1, a microglia-specific marker, significantly increased in the hippocampus and its surrounding area in mice after three weeks of infection, and then became pronounced after four weeks of infection; while YM-1, an eosinophilic chemotactic factor, in the hippocampus and midbrain, increased significantly from two weeks post-infection, sharply escalated after three weeks of infection, and peaked after four weeks of infection. Cytometric bead array (CBA) analysis revealed that the expression of TNF in the serum of mice increased concomitantly with the prolongation of infection duration. Furthermore, IFN-γ and IL-4 in rat serum were significantly higher than in mouse serum at two weeks post-infection, indicating significantly different immune responses in the brains of rats and mice. We suggest that 18F-FDG uptake in the host brain may be attributed to the accumulation of large numbers of immune cells, especially the metabolic burst of activated eosinophils, which are attracted to and induced by activated microglia in the brain. CONCLUSIONS: An in vivo 18F-FDG/PET imaging model can be used to evaluate live neuroinflammatory pathological changes in the brains of A. cantonensis-infected mice and rats.

Interactions of chemical components in ambient PM2.5 with influenza viruses.

The significance of this work is that ambient PM2.5 is a direct transmission mode for influenza virus infection to the human alveolar epithelium. The concentration of PM2.5 was 11.7 ± 5.5 µg/m3 in Taipei during 24 December 2019-13 January 2020. Approximately 79% of inhaled PM2.5 is able to reach the upper-to-lower airway, and 47% of PM2.5 is able to reach the alveolar epithelium for influenza virus infection. Influenza A and B viruses were detected in PM2.5 on 9 days, and the influenza A/H5 virus was detected on 15 days during the study period. FL and Pyr were negatively correlated with the influenza A virus. D(ah)P and Acp were positively correlated with the influenza B and A/H5 viruses, respectively. Cd, V, and Zn were positively correlated with the influenza A, B, and A/H5 viruses, respectively. Next, influenza A, B, and A/H5 viral plasmids interacted with carbon black, H2O2, DEPs, and UD. We observed that H2O2 significantly decreased levels of complementary DNA of the three influenza viruses. DEPs and UD significantly decreased influenza A and A/H5 viral levels. In conclusion, chemicals in PM2.5 may play vital roles in terms of viable influenza virus in the atmosphere.

Schistosoma egg antigens suppress LPS-induced inflammation in human IMR-90 cells by modulation of JAK/STAT1 signaling.

BACKGROUND: The regulation of the balance between inflammatory and anti-inflammatory events during the treatment of pulmonary infection is very important. Soluble Schistosoma egg antigens (SEA) can effectively inhibit the expression of cytokines during hepatic acute inflammation. However, the mechanisms by which these proteins suppress the inflammatory responses in lung cells remain unclear. The purpose of this study was to investigate the ability of SEA to inhibit pulmonary inflammation. METHODS: The effects of SEA were investigated in LPS-treated lung IMR-90 cells. The involvement of the JAK/STAT-1 signaling pathway in these effects was evaluated by employing CBA assays, quantitative polymerase chain reaction, and western blotting experiments. RESULTS: Pretreatment of IMR-90 cells with appropriate concentrations of SEA protected cells against the cytotoxic effects of LPS-induced inflammation in a time-dependent manner. SEA pretreatment significantly attenuated the LPS-induced activation of the JAK/STAT1 signaling pathway, including the upregulation of JAK1/2 and STAT1, as well as the production of inflammatory cytokines. The level of phosphorylated STAT1 gradually declined in response to increasing concentrations of SEA. Based on these findings, we hypothesize that SEA-induced anti-inflammatory effects initiate with the downregulation of the IFN-γ-JAK-STAT1 signaling pathway, resulting in the attenuation of LPS-induced inflammation in IMR-90 cells. CONCLUSION: Our study is the first to demonstrate the anti-inflammatory activity of SEA in an in vitro model of pulmonary inflammation, involving the modulation of JAK/STAT1 signaling. We propose SEA as potential therapeutic or preventive agents for the selective suppression of STAT1 and the control of inflammatory response in lung IMR-90 cells.