| dc.description | 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. | |
