The Role of Platelets in Malarial Acute Lung Injury and Acute Respiratory Distress Syndrome: A World of Possibilities.

In recent decades our understanding of platelets’ role in immune response has increased. Traditionally platelets were considered as bleeding-stopping and thrombosis-causing cells. In recent years the platelets’ role in malarial innate and adaptive immune responses is being recognized. Platelets play critical role in pathogenesis of malaria infection leading to variety of outcomes. It is being realized that platelets play dual role in case of malaria (i) by preventing early stage exponential growth of parasitemia (ii) promoting exaggerated immune responses later. Platelets role in pathogenesis of severe and cerebral malaria has been widely studied. However their role in malaria related acute lung injury and respiratory distress has gained less attention. Recently the presence of active megakaryocytes and proplatelets have been explained in human lungs. Simultaneously, the platelets role in pathogenesis of acute lung injury and respiratory distress (ALI/ARDS) was also recognized. This gives a hint that there is a possible association of platelets with malaria related respiratory diseases as well. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. In this review we have attempted to establish the importance of role of platelets in malaria related acute lungs injury and malaria acute respiratory distress syndrome and try to explain the underlying mechanism of this process. In ALI/ARDS, including those caused by malaria, platelets participate sequestration to the vascular bundle facilitating the recruitment of immune cells viz. neutrophils. Additionally, they secrete or induce the secretion of chemokines that result into vascular damage.

Humoral immune IgG response to Plasmodium falciparum in adults: the role of subclass-IgG in clinical immunity to cerebral Malaria

Although antibodies are essential mediators of immunity, high levels of IgG antibodies against a wide range of blood-stage antigens of P. falciparum are poor predictors of clinical protection. It is the qualitative and the functional specificity of the antibodies to malaria antigens that predict the development of a clinically potent protective immunity. The objective of this work is to study the pattern of IgG sub-class in healthy and malaria-infected adults resident in a malaria-endemic area in Sudan. Total plasma IgG and IgG subclasses [IgG1, 2, 3 and 4] against the C-terminal region of the MSA-1[19] antigen of Plasmodium falciparum were measured by a quantitative enzyme-linked immunosorbent assay [ELISA] in 30 adult patients presenting to the emergency department with cerebral malaria [CM]. The levels of IgG antibody profile in CM patients were compared with those in patients with uncomplicated acute malaria [n=20] and in clinically healthy asymptomatic volunteers [n=20]. Total plasma IgG level was significantly higher in CM patients. The level of the sub-class IgG1 antibody against MSA-119 was significantly lower in patients infected with P. falciparum; the lowest values being observed in CM patients and the highest values in the clinically healthy volunteers. Our data suggest that acquisition of IgG1 antibody to MS A-1[19] is associated with a clinically protective immunity and that low production or defective IgG1 response may be associated with severe form of malaria in adults

Plasmodium berghei ANKA infection induces thymocyte apoptosis and thymocyte depletion in CBA mice

Immune responses to malaria infections are characterized by strong T and B cell activation, which, in addition of potentially causing immunopathology, are of poor efficacy against the infection. It is possible that the thymus is involved in the origin of immunopathological reactions and a target during malaria infections. This work was developed in an attempt to further clarify these points. We studied the sequential changes in the thymus of CBA mice infected with Plasmodium berghei ANKA, a model in which 60-90 percent of the infected animals develop cerebral malaria. During the acute phase of infection, different degrees of thymocyte apoptosis were recorded: (1) starry-sky pattern of diffuse apoptosis with maintenance of cortical-medullary structure; (2) intense apoptosis with cortical atrophy, with absence of large cells; (3) severe cortical thymocyte depletion, resulting in cortical-medullary inversion. In the latter, only residual clusters of small thymocytes were observed within the framework of epithelial cells. The intensity of thymus alterations could not be associated with the degree of parasitemia, the expression of clinical signs of cerebral malaria or intensity of brain lesions. The implications of these events for malaria immunity and pathology are discussed.

Cytokines associated with pathology in the brain tissue of fatal malaria.

Cytoadherence of Plasmodium falciparum-infected erythrocytes to the brain microvascular endothelial cells is believed to be an important cause of circulatory blockage in cerebral malaria. Cytokines released during acute infection may activate brain endothelial cells leading to increased binding of infected erythrocytes in the brain and reduced cerebral blood flow. This effect may be direct and more potent with the tissue-localized cytokines in the brain. In order to establish this relationship, brain tissues of cerebral and noncerebral malaria were compared. The most prominent histopathologic changes in the brain included edema, neuronal degeneration, ring hemorrhage, and percentage of parasitized erythrocytes sequestration were observed in cerebral malaria. Immunohistochemical staining of the brain sections demonstrated that tissue-localized TNF-alpha, IFN-gamma, IL-I1B, and IL-10 were associated with the histopathology. However, IL-4 was the only cytokine presented at moderate level in the brain tissue of noncerebral malaria which histopathology was the least. No tissue-localized cytokine was observed in the brain of P. vivax infection or of the car accident control cases.