Clinical Microbiology: Open Access

Infection of Erythrocytes by Plasmodium falciparum

Martin Danis^* Department of Microbiology and Immunology, National University of Singapore, Singapore
^*Correspondence: Martin Danis, Department of Microbiology and Immunology, National University of Singapore, Singapore, Email:

Received: 01-Jun-2022, Manuscript No. CMO-22-17354; Editor assigned: 06-Jun-2022, Pre QC No. CMO-22-17354(PQ); Reviewed: 22-Jun-2022, QC No. CMO-22-17354; Revised: 27-Jun-2022, Manuscript No. CMO-22-17354(R); Published: 04-Jul-2022, DOI: 10.35248/2327-5073.22.11.291

Description

The generation of cytokines and the cytoadherence of parasitized red blood cells (PRBCs) to postcapillary venules are implicated in Plasmodium falciparum infection that causes cerebral malaria. We show that human endothelial cells undergo death when PRBC adherence occurs (HLECs). Tumor necrosis factor superfamily genes (Fas, Fas L, and DR-6) and apoptosis-related genes (Bad, Bax, caspase-3, SARP 2, DFF45/ICAD, IFNreceptor 2, Bcl-w, Bik, and iNOS) were affected by PRBC adherence in HLEC. Using electron microscopy, morphological changes, annexin V binding, DNA destruction (measured by intracytoplasmic nucleosomes), and caspase activity were used to confirm apoptosis. Physical contact between HLECs and PRBCs, not chemicals released by the parasite, provided the apoptotic stimulus. Furthermore, it was discovered that this mechanism involves both mitochondrial (caspase 9) and cytoplasmic (caspase 8) pathways. These findings not only outline the direct apoptotic impact of PRBC adhesion on endothelial cells, but they also offer fresh, practical tools for assessing potential medicines.

Severe clinical illness is caused by the cytoadherence of Plasmodium falciparum-infected erythrocytes (PRBC) to endothelial cells, most likely as a result of perfusion failure and tissue hypoxia. Endothelial cell activation, which is thought to happen in a paracrine manner by mediators such Tumour Necrosis Factor alpha (TNF), produced from macrophages that initially identify PRBC, increases cytoadherence to endothelial cells. Here, we present evidence that, in the absence of macrophages, PRBC directly stimulate human endothelial cells, increasing the expression of molecules that promote adhesion, such as intercellular adhesion molecule 1. For a brief period of time (30 min to 60 min), direct physical contact was necessary for PRBC to stimulate endothelial cells, and parasitemia was connected to this. Chemokine and adhesion molecule gene expression levels were higher in endothelial cells activated by PRBC, according to gene expression profiling. Even following TNF-challenge, PRBC-stimulated endothelial cells failed to express molecules that promote leukocyte adherence, such as E-selectin and vascular cell adhesion molecule 1. Instead, they enhanced the production of molecules implicated in parasite adhesion. Collectively, our observations imply that PRBC stimulation of endothelial cells may have two effects: reducing leukocyte attachment to endothelial cells to reduce immunological reactivity and limiting parasite clearance through increased cytoadherence.

The falciparum malaria parasite alters the surface of infected red blood cells, causing them to cling to other red blood cells and vascular endothelium. As a result, the ring stages of Plasmodium falciparum circulate in the blood stream while the more mature stages are contained in the microvasculature and lead to the malfunctioning of critical organs. Fever is a feature of malaria. We looked at how febrile temperatures affected the in vitro cytoadherence of P. falciparum infected erythrocytes. Ten patients with acute falciparum malaria had freshly collected ring-stageinfected red blood cells, however they did not cling to the main vascular adherence receptors CD36 or Intercellular Adhesion Molecule-1 (ICAM-1). However, all ring-infected red blood cells attached to CD36 and some isolates adhered to ICAM-1 after a brief period of heating to 40°C, whereas controls incubated at 37°C did not. The maximal amount of cytoadherence was doubled and accelerated by heating to 40°C (P 0.01). When heated to feverish temperatures, erythrocytes infected by ringstages of the ICAM-1-binding clone A4var adhered to both CD36 and ICAM-1 but did not cytoadhere at 37°C. The brief heating also greatly boosted the adhesion of red blood cells infected with trophozoites. The parasite-derived mutant surface protein PfEMP-1 was found to be the cause of heat-induced adhesion. A RNA study revealed that the amounts of var mRNA in warm and unheated ring-stage parasites were the same. Therefore, enhanced PfEMP-1 trafficking to the erythrocyte membrane seems to be a contributing factor in fever-induced adhesion. The clinical worsening that comes with fever in cases of severe malaria and the effects of antipyretics on parasite clearance could both be explained by fever-induced cytoadherence, which is likely to have significant pathological repercussions.

EBV and P. falciparum, two cunning pathogens, can alter how cells involved in maintaining the integrity of the BBB operate. In our investigation, endothelial activation brought about by EBV infection boosted the expression of endothelial surface markers. This might encourage leukocyte extravasation and migration at the infection site. The migration of uninfected ECs, glial cells, and neuronal cells was impacted by EBV infection of BBB ECs. This can be linked to a decreased glial cell response to infection at the BBB location, which could compromise the integrity of the BBB. Compared to monoinfection settings, RBC adherence to ECs was substantially higher during the P. falciparum and EBV dual infection scenario. This might make it easier for iRBCs to get trapped at the BBB, aggravating CM pathology. The research into the potential role of EBV in CM pathology may soon be intensified as a result of the new direction our report provides.