Plasmodium parasites need to find red blood cells (RBCs) that, on the one hand, expose receptors for the pathogen ligands and, on the other hand, maintain the right geometry to facilitate merozoite attachment and entry into the red blood cell. Both characteristics change with the maturation of erythrocytes. Some Plasmodia prefer younger vs. older erythrocytes. How does the life evolution of the RBC affect the invasion of the parasite? What happens when the RBC ages? In this review, we present what is known up until now.

Pathological processes often change the mechanical properties of cells. Increased rigidity could be a marker of cellular malfunction. Erythrocytes are a type of cell that deforms to squeeze through tiny capillaries; changes in their rigidity can dramatically affect their functionality. Furthermore, differences in the homeostatic elasticity of the cell can be used as a tool for diagnosis and even for choosing the adequate treatment for some illnesses. More accurate types of equipment needed to study biomechanical phenomena at the single-cell level are very costly and thus out of reach for many laboratories around the world. This study presents a simple and low-cost technique to study the rigidity of red blood cells (RBCs) through the application of electric fields in a hand-made microfluidic chamber that uses a capacitor principle. As RBCs are deformed with the application of voltage, cells are observed under a light microscope. From mechanical force vs. deformation data, the elastic constant of the cells is determined. The results obtained with the capacitor-based method were compared with those obtained using optical tweezers, finding good agreement. In addition, P. falciparum-infected erythrocytes were tested with the electric field applicator. Our technique provides a simple means of testing the mechanical properties of individual cells.

Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical illness affecting 6–8 million people in Latin America. Reaching scholarly consensus on the host response to T. cruzi infection remains a significant challenge, primarily due to substantial heterogeneity in outcomes driven by both the choice of animal model and the infecting parasite’s discrete typing unit (DTU). This variability complicates the evaluation and comparison of new therapeutic compounds against existing drugs, namely benznidazole and nifurtimox. This study provides a comprehensive, kinetic, multifaceted characterization of the acute infection using the highly virulent T. cruzi Y strain (TcII) in outbred Swiss mice. Here, crucial infection parameters are presented, including the optimal infective dose, the parasitemia dynamics, tissue damage markers, hematological profiles, cytokine production (Th1/Th2/Th17/Th22), and molecular parasite identification in target organs (heart, colon, esophagus, spleen, and liver) across the span of the infection. The novelty of this study lies in the kinetic integration of these parameters within a defined model; rather than presenting isolated data points, we demonstrate how the biochemical, physiological, and clinical signs and immunological responses, with the resulting organ involvement, evolve and interact over time. To complete the report, a necropsy evaluation was performed at the end of the acute, fatal infection, and it is presented here. This study fulfills a long-standing recommendation from diverse drug discovery groups for the creation of a definitive reference model to standardize preclinical testing for anti-Chagasic agents.

Programmed cell death pathways in Plasmodium falciparum remain conceptually fragmented. Over decades, researchers have applied metazoan apoptotic, autophagic, and necrotic markers to this deep-branching protozoan, frequently clashing with the reality that the parasite lacks the canonical genetic machinery (such as true caspases or death receptors) found in multicellular eukaryotes. In this work, we shift the focus from the parasite’s disputed intrinsic death machinery to a neglected arena: the active manipulation of the host erythrocyte’s autonomous suicide program, eryptosis. We integrate existing literature on membrane remodeling, protein export, and lipid raft dynamics to propose a novel Host Protein Sequestration Hypothesis. We suggest that P. falciparum evades splenic clearance by actively dismantling the host cell’s surface death signaling platforms—Clusters of Apoptotic Signaling Molecule-Enriched Rafts (CASMERs)—and pulling these host components inward. We suggest that human FAS is internalized by the parasite and physically interacts with Plasmodium lipid-raft scaffolding proteins. This perspective offers a fundamentally fresh conceptual framework for understanding malaria survival strategies and highlights a vulnerable, non-canonical therapeutic target.

Programmed cell death pathways in Plasmodium falciparum remain conceptually fragmented. Over decades, researchers have applied metazoan apoptotic, autophagic, and necrotic markers to this deep-branching protozoan, frequently clashing with the reality that the parasite lacks the canonical genetic machinery (such as true caspases or death receptors) found in multicellular eukaryotes. In this work, we shift the focus from the parasite’s disputed intrinsic death machinery to the host–parasite interaction arena: the active manipulation of the host erythrocyte’s autonomous suicide program, eryptosis. The intraerythrocytic development of P. falciparum generates profound oxidative stress through hemoglobin digestion and free heme release, driving lipid peroxidation and the accumulation of reactive aldehydes such as 4-hydroxynonenal (4-HNE)—potent signaling molecules that can trigger eryptotic pathways. We integrate existing literature on membrane remodeling, protein export, and lipid raft dynamics to propose a novel Host Protein Sequestration Hypothesis. We suggest that P. falciparum evades splenic clearance by actively dismantling the host cell’s surface death signaling platforms—Clusters of Apoptotic Signaling Molecule-Enriched Rafts (CASMERs)—and pulling these host components inward. We suggest that human FAS (CD95) is internalized by the parasite and physically interacts with Plasmodium lipid-raft scaffolding proteins, preventing it from engaging FasL (CD178) that is either expressed on adjacent erythrocytes or presented within the local splenic microenvironment—an interaction that would otherwise precipitate eryptotic signaling. This perspective offers a fundamentally fresh conceptual framework for understanding malaria survival strategies and highlights a vulnerable, non-canonical therapeutic target.