Splenic architecture disruption and parasite-induced splenocyte activation and anergy in Plasmodium falciparum-infected Saimiri sciureus monkeys

BACKGROUND: The understanding of the mechanisms of immunity in malaria is crucial for the rational development of interventions such as vaccines. During blood stage infection, the spleen is considered to play critical roles in both immunity and immunopathology of Plasmodium falciparum infections. METHODS: Saimiri sciureus monkeys were inoculated with blood stages of P. falciparum (FUP strain) and spleens removed during acute disease (days 7 and 13 of infection) and during convalescence (15 days after start of chloroquine treatment). Cytokine (IFNγ, TNFα, IL2, IL6, IL10, and IL12) responses of splenocytes stimulated with P. falciparum-parasitized red blood cells were assessed by real-time PCR using specific Saimiri primers, and histological changes were evaluated using haematoxylin-eosin and Giemsa-stained slides. RESULTS: Early during infection (day 7, 1-2% parasitaemia), spleens showed disruption of germinal centre architecture with heavy B-cell activation (centroblasts), and splenocytes showed increased expression of IFNγ, IL6 and IL12 upon in vitro stimuli by P. falciparum-parasitized red blood cells (pRBC). Conversely, 15 days after treatment of blood stage infection with chloroquine, splenocytes showed spontaneous in vitro expression of TNFα, IL2, IL6, IL10, and IL12, but not IFNγ, and stimulation with P. falciparum pRBC blocked the expression of all these cytokines. During the acute phase of infection, splenic disarray with disorganized germinal centres was observed. During convalescence, spleens of the chloroquine-treated animals showed white pulp hyperplasia with extensive lymphocyte activation and persistency of heavily haemozoin-laden macrophages throughout the red pulp. CONCLUSIONS: Inability to eliminate haemozoin is likely involved in the persistent lymphocyte activation and in the anergic responses of Saimiri splenocytes to P. falciparum pRBC, with important negative impact in immune responses and implications for the design of malaria vaccine

Overview on cell-biomaterial interactions

Biomaterials, a name given to express materials used as medical implants, indwelling devices, extracorporeal ones and other categories in several medical fields, have increasingly played a significant role when aiming at improving the quality of life in humans. The behavior of a biomaterial with the surrounding physiologic environment is of major relevance for determining the in vivo performance and host acceptance of any device. Indeed, the biocompatibility and bio-functionality of implantable devices remains a serious challenge in establishing the devices function and lifetime. Several research efforts have been conducted to further understand and control the interactions between biomaterials and cell-mediated processes, aiming at the definition of the main guidelines that regulate materials biocompatibility. Several criteria should be met when considering a biomaterial for a specific application. On the materials perspective, its composition, mechanical, physicochemical, thermal, electrical properties must be well understood. In parallel, knowledge on the cell-biomaterial interaction mechanisms (including specific adhesion proteins and cell receptors, signal transduction, cell differentiation, tissue development, host immune response mechanisms, to name a few processes) must be attained, to better characterize, follow up and control cell-biomaterial interactions. This review attempts to define the basic phenomenon that take place when a biomaterial comes into contact with host living tissues. Numerous strategies have been investigated to overcome body reactions induced by the implantation of devices. These strategies, their advantages and limitations, along with the fundamentals underlying biomaterials-tissue interactions and current research on biomaterial surface modification are discussed. Besides, the use of polymeric biomaterials for use in age-related macular degeneration will be presented as a case study