The Ins and Outs of Cerebral Malaria Pathogenesis: Immunopathology, Extracellular Vesicles, Immunometabolism, and Trained Immunity

Conclusion and Future Directions The ECM model has produced a wealth of information on CM pathogenesis in mice with the aim to find an adjunctive therapy for HCM but its validity has been questioned. However, several investigators have provided a critical and evidence-based defense of this model (17, 128–131) and from knowledge gained from it, numerous laboratories have tested preclinical therapeutic interventions. Many have demonstrated efficacy at blocking the development of ECM but disappointingly, in a majority of cases, this was only found when administered before or early post infection and prior to the onset of clinical neurological signs. Therefore, only a few can justify, as therapies, a large-scale evaluation in HCM. A rare case of efficacy of treatment even when administered after the onset of clinical signs in the ECM model is the injection of IMP (52). The only other studies to date having demonstrated treatment efficacy after the onset of ECM have targeted CD8+ T cell binding to endothelial cells, and finally, immunometabolism. These successes have renewed hopes that the mouse model of ECM will continue to bring novel ideas/concepts which then will need to be confirmed or infirmed in HCM. For example, the characterization of retinal pathology in ECM (132) and (133), which was followed by the demonstration of its usefulness in HCM (134–137) (and many others) or MRI findings of brain alterations, originally described in 2005 for ECM (97), and ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research