Interactions between dendritic cells and CD4+ T cells during Plasmodium infection

<p>Abstract</p> <p>Background</p> <p>During infection, dendritic cells (DCs) encounter pathogenic microorganisms that can modulate their function and shape the T cell responses generated. During the process of T cell activation, DCs establish strong, long-lasting interactions with naïve T cells.</p> <p>Methods</p> <p>Using a mouse malaria model, the interactions of DCs and naïve CD4⁺T cells have been analysed.</p> <p>Results</p> <p>DCs, either incubated <it>in vitro </it>with infected erythrocytes or isolated from infected mice, are able to present exogenous antigens by MHC-II, but are not able to establish prolonged effective interactions with naïve CD4⁺T cells and do not induce T cell activation. It was also found that effective T cell activation of naïve CD4⁺T cells is impaired during late <it>Plasmodium yoelii </it>infection.</p> <p>Conclusion</p> <p>These data may provide a mechanism for the lack of effective adaptive immune responses induced by the Plasmodium parasite.</p

Malaria Blood Stage Suppression of Liver Stage Immunity by Dendritic Cells

Malaria starts with Plasmodium sporozoites infection of the host's liver, where development into blood stage parasites occurs. It is not clear why natural infections do not induce protection against the initial liver stage and generate low CD8+ T cell responses. Using a rodent malaria model, we show that Plasmodium blood stage infection suppresses CD8+ T cell immune responses that were induced against the initial liver stage. Blood stage Plasmodium affects dendritic cell (DC) functions, inhibiting maturation and the capacity to initiate immune responses and inverting the interleukin (IL)-12/IL-10 secretion pattern. The interaction of blood stage parasites with DCs induces the secretion of soluble factors that inhibit the activation of CD8+ T cells in vitro and the suppression of protective CD8+ T cell responses against the liver stage in vivo. We propose that blood stage infection induces DCs to suppress CD8+ T cell responses in natural malaria infections. This evasion mechanism leaves the host unprotected against reinfection by inhibiting the immune response against the initial liver stage of the disease

Dual effect of Plasmodium-infected erythrocytes on dendritic cell maturation

<p>Abstract</p> <p>Background</p> <p>Infection with <it>Plasmodium </it>is the cause of malaria, a disease characterized by a high inflammatory response in the blood. Dendritic cells (DC) participate in both adaptive and innate immune responses, influencing the generation of inflammatory responses. DC can be activated through different receptors, which recognize specific molecules in microbes and induce the maturation of DC.</p> <p>Methods</p> <p>Using <it>Plasmodium yoelii</it>, a rodent malaria model, the effect of <it>Plasmodium</it>-infected erythrocytes on DC maturation and TLR responses have been analysed.</p> <p>Results</p> <p>It was found that intact erythrocytes infected with <it>P. yoelii </it>do not induce maturation of DC unless they are lysed, suggesting that accessibility of parasite inflammatory molecules to their receptors is a key issue in the activation of DC by <it>P. yoelii</it>. This activation is independent of MyD88. It was also observed that pre-incubation of DC with intact <it>P. yoelii</it>-infected erythrocytes inhibits the maturation response of DC to other TLR stimuli. The inhibition of maturation of DC is reversible, parasite-specific and increases with the stage of parasite development, with complete inhibition induced by schizonts (mature infected erythrocytes). <it>Plasmodium yoelii</it>-infected erythrocytes induce a broad inhibitory effect rendering DC non-responsive to ligands for TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9.</p> <p>Conclusions</p> <p>Despite the presence of inflammatory molecules within <it>Plasmodium</it>-infected erythrocytes, which are probably responsible for DC maturation induced by lysates, intact <it>Plasmodium</it>-infected erythrocytes induce a general inhibition of TLR responsiveness in DC. The observed effect on DC could play an important role in the pathology and suboptimal immune response observed during the disease. These results help to explain why immune functions are altered during malaria, and provide a system for the identification of a parasite-derived broad inhibitor of TLR-mediated signaling pathways.</p