Plasmodium infection and dysbiosis: A new paradigm in the host-parasite interaction.

The mucosal immune system contributes for the largest component of the tissue immune system due to its massive surface area and constant exposure to the microbiota. The gut microbiota comprises a complex micro-ecosystem in the intestine and plays a major role in regulating innate and adaptive immunity. Several studies revealed that infectious diseases involve bidirectional interactions in the gut microenvironment, including changes in the gut microbiota composition. During Plasmodium infection, an increase of pro-inflammatory cells in the lamina propria and a shift in the composition of the gut microbiota contribute to intestinal ecosystem dysbiosis. Although the mechanisms of this dysbiosis is still uncertain, it is thought to be associated with the sequestration of infected red blood cells in the intestinal microvascular system, leading to endothelial villous disruption, and thus activating effector immune cells scattered in the intestinal epithelium and lamina propria. This review provides information on this conjoint interaction which will be beneficial to modulate the host immune response in malaria through manipulation of the gut microbiota composition.

Bifidobacterium longum Administration Diminishes Parasitemia and Inflammation During Plasmodium berghei Infection in Mice.

Purpose: During Plasmodium berghei (P. berghei) infection, infected erythrocytes are sequestered in gut tissues through microvascular circulation, leading to dysbiosis. This study aimed to investigate the effect of Lactobacillus casei (L. casei) and Bifidobacterium longum (B. longum) administration on the parasitemia level, gut microbiota composition, expression of cluster of differentiation 103 (CD103) in intestinal dendritic and T regulatory cells (T reg), plasma interferon gamma (IFN-γ) and tumor necrosis factor (TNF-α) levels in P. berghei infected mice. Methods: P. berghei was inoculated intraperitoneally. Infected mice were randomly divided into 5 groups and treated with either L. casei, B. longum, or the combination of both for 5 days before up to 6 days post-infection (p.i). The control group was treated with phosphate-buffered saline (PBS), while uninfected mice were used as negative control. Levels of CD103 and forkhead box P3 (FoxP3) expression were measured by direct immunofluorescense, while plasma IFN-γ and TNF-α level were determined using enzyme-linked immunosorbent assay (ELISA). Results: All treated groups showed an increase in parasitemia from day 2 to day 6 p.i, which was significant at day 2 p.i (p = 0.001), with the group receiving B. longum displaying the lowest degree of parasitemia. Significant reduction in plasma IFN-γ and TNF-α levels was observed in the group receiving B. longum (p = 0.022 and p = 0.026, respectively). The CD103 and FoxP3 expression was highest in the group receiving B. longum (p = 0.01 and p = 0.02, respectively). Conclusion: B. longum showed the best protective effect against Plasmodium infection by reducing the degree of parasitemia and modulating the gut immunity. This provides a basis for further research involving probiotic supplementation in immunity modulation of infectious diseases.