Strain-specific spleen remodelling in Plasmodium yoelii infections in Balb/c mice facilitates adherence and spleen macrophage-clearance escape

Abstract

Knowledge of the dynamic features of the processes driven by malaria parasites in the spleen is lacking. To gain insight into the function and structure of the spleen in malaria, we have implemented intravital microscopy and magnetic resonance imaging of the mouse spleen in experimental infections with non-lethal (17X) and lethal (17XL) Plasmodium yoelii strains. Noticeably, there was higher parasite accumulation, reduced motility, loss of directionality, increased residence time and altered magnetic resonance only in the spleens of mice infected with 17X. Moreover, these differences were associated with the formation of a strain-specific induced spleen tissue barrier of fibroblastic origin, with red pulp macrophage-clearance evasion and with adherence of infected red blood cells to this barrier. Our data suggest that in this reticulocyte-prone non-lethal rodent malaria model, passage through the spleen is different from what is known in other Plasmodium species and open new avenues for functional/structural studies of this lymphoid organ in malaria.

Spleen Rupture in a Case of Untreated Plasmodium vivax Infection

“…Although it is plausible that some of these parasites were simply detected in their passage through the spleen, it is difficult to reconcile this sole explanation with the large numbers detected and the co-localization studies demonstrating that they were mostly outside macrophages. Noticeably, cytoadherence of the reticulocyte-prone nonlethal P. yoelii 17× strain to a spleen blood barrier of fibroblastic origin has been shown [23]. Most important, cytoadherence of P. vivax –infected reticulocytes to different endothelial receptors have been recently demonstrated [24], [25].…”

Disorganization of the splenic microanatomy in ageing mice

“…The higher basal level of antibody reactivity that was observed in old mice may be due to the age-associated increase in autoantibody production. 44 Interestingly, studies have shown that some parasitic 45,46 and viral 47,48 infections can directly cause significant disruption of the splenic architecture, resulting in the inability of the host to mount a robust immune response, suggesting that this may be a potential mechanism used by pathogens to reduce immune efficacy and increase pathogenesis. Hence, the age-associated disruption of the splenic architecture may reflect the accumulation of remodelling due to the continual antigenic challenge of the host, which over time might impact on the structural integrity of SLO.…”

“…Corroboratively, the studies highlighting splenic remodelling and the efficacy of the immune response, [46][47][48] indicate a correlation between the structural integrity of the splenic microenvironment and immune competency. 16 As previously mentioned, adoptive transfer experiments demonstrated altered trafficking of young lymphocytes within the aged spleen.…”

Intravital microscopy: Imaging host–parasite interactions in lymphoid organs

“…The non‐lethal strain, however, displayed an adhesive rolling‐circle behaviour, while the lethal strain did not. Conversely, FITC‐labelled uninfected RBCs and fluorescent beads displayed equal flow patterns in mice infected with either strain (Martin‐Jaular et al, ) (Fig. 3Bi).…”

“…Primary image shows the spleen of a mouse infected with non‐lethal P. yoelii 17X (green) at day 3 post‐infection, showing FGF8 as a marker of a barrier of fibroblastic origin (red) and F4/80 macrophages (blue). (Adapted from Martin‐Jaular et al, ). (Bii) shows that at early synchronised infections, P. berghei ANKA schizonts sequester in the vascular periphery, avoiding the spleen, while parasites unable to sequester (Pb∆MAHRP1a and Pb∆SBP1) are absent from the vasculature in the periphery, but are present in vast numbers in the spleen, where they are eliminated.…”