Background: Pulmonary oedema (PE) is a serious complication of Plasmodium falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex hostimmune response. The molecular basis for macrophage polarization is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarization of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients, with and without evidence of PE. Methods: Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorized into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68+, all macrophages; CD40+, M1 macrophage; and CD163+, M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. Results: Lung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (63.44 ± 1.98%), compared to non-PE group (53.22 ± 3.85%, p < 0.05), whereas there was no difference observed for CD163 (M2 macrophage) between PE and non-PE groups. Conclusions: The study demonstrates M1 polarization in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterization in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria.

Background Cerebral malaria (CM) is associated with sequestration of parasitized red blood cells (PRBCs) in the capillaries. Often, the association of CM with cerebral oedema is related with high mortality rate. Morphological changes of the choroid plexus (CP) and caspase-3 expression in CM have not been reported. In addition, limited knowledge is known regarding the role of aquaporin (AQP)-1 in CM. The present study evaluated changes in the CP, explored apoptotic changes and AQP-1 expression in CP epithelial cells (CPECs) in fatal CM patients. Methods CP from fatal Plasmodium falciparum malaria patients (5 non-CM [NCM], 16 CM) were retrieved and prepared for histopathological evaluation. Caspase-3 and AQP-1 expressions in CPECs were investigated by immunohistochemistry. Results Histologically, apoptotic changes in CPECs were significantly observed in the CM group compared with the NCM and normal control (NC) groups (p < 0.05). These changes included cytoplasmic and nuclear condensation/shrinkage of CPECs and detachment of CPECs from the basement membrane. The apoptotic changes were positively correlated with caspase-3 expression in the nuclei of CPECs. In addition, AQP-1 expression in CPECs was significantly decreased in the CM group compared with the NCM and NC groups (all p < 0.001). A negative correlation (rs =  − 0.450, p = 0.024) was documented between caspase-3 expression in the nuclei of CPECs and AQP-1. Conclusions Apoptotic changes and altered AQP-1 expression may contribute to CPEC dysfunction and subsequently reduce cerebrospinal fluid production, affecting the water homeostasis in the brains of patients with CM.

Background: We aimed to determine whether neutralizing high mobility group box-1 (HMGB-1) prevents the release of HMGB-1 and proinflammatory cytokines on hemozoin (Hz)-induced alveolar epithelial cell in a model of malaria associated ALI/ARDS. Methods: This study was conducted in the Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand in 2020. Human pulmonary alveolar epithelial cells (HPAEpiCs) were exposed to medium alone or 20 µM Hz for 24 h and incubated with different concentrations (1, 5, and 10 µg/ml) of anti-HMGB-1 monoclonal antibody (mAb) for various times (0, 4, 12, 24, and 48 h). The levels of HMGB-1, TNF-α and IFN-γ in the supernatants were measured by ELISA. The mRNA expression of RAGE, TLR-2 and TLR-4 were analyzed by real-time PCR. Results: The HPAEpiCs treated with 10 µg/ml anti-HMGB-1 mAb showed a significant reduction in HMGB-1 release into the supernatant compared with those treated with 1 and 5 µg/ml anti-HMGB-1 mAb. The levels of TNF-α and IFN-γ were significantly decreased in the supernatant of HPAEpiCs treated with 1, 5, and 10 µg/ml anti-HMGB-1 mAb for 4, 12, 24, and 48 h compared with those stimulated with Hz alone. The mRNA expression levels of RAGE, TLR-2, and TLR-4 were significantly decreased after 24 h of anti-HMGB-1 antibody treatment at all concentrations. Conclusions: An anti-HMGB-1 antibody could be an effective agent for inhibiting the release of HMGB-1, TNF-α and IFN-γ. Furthermore, a neutralizing anti-HMGB-1 antibody could be applicable for the treatment of malaria-associated ALI/ARDS.