Plasmodium sporozoites trickle out of the injection site

Plasmodium sporozoites make a remarkable journey from the skin, where they are deposited by an infected Anopheline mosquito, to the liver, where they invade hepatocytes and develop into exoerythrocytic stages. Although much work has been done to elucidate the molecular mechanisms by which sporozoites invade hepatocytes, little is known about the interactions between host and parasite before the sporozoite enters the blood circulation. It has always been assumed that sporozoites rapidly exit the injection site, making their interactions with the host at this site, brief and difficult to study. Using quantitative PCR, we determined the kinetics with which sporozoites leave the injection site and arrive in the liver and found that the majority of infective sporozoites remain in the skin for hours. We then performed sub-inoculation experiments which confirmed these findings and showed that the pattern of sporozoite exit from the injection site resembles a slow trickle. Last, we found that drainage of approximately 20% of the sporozoite inoculum to the lymphatics is associated with a significant enlargement of the draining lymph node, a response not observed after intravenous inoculation. These findings indicate that there is ample time for host and parasite to interact at the inoculation site and are of relevance to the pre-erythrocytic stage malaria vaccine effort

Mycobacterium bovis bacillus Calmette-Guerin treated human cord blood monocyte-derived dendritic cells polarize naïve T cells into a tolerogenic phenotype in newborns

Background: As one of the first infectious challenges of life, the impact of neonatal Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccination on the polarization of neonatal T helper subset has not been well defined. Methods: We investigated the effect of BCG-treated cord blood (CB) dendritic cells (DCs) on naïve CD4+ T cells polarization compared with that of adult blood DCs. Results: BCG-treated CB DCs had significantly lower expression of CD83 and a higher ratio of CD47/Fas than BCG-treated adult blood DCs. BCG induced significantly lower IL-12 but relatively higher IL-10 production from CB DCs than adult blood DCs. Moreover, in comparison with BCG-treated adult blood DCs, BCG-treated CB DCs induced higher IL-10 production and cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression, and lower interferon-gamma (IFN-γ) production from naïve CD4+ T cells. On the other hand, lipopolysaccharide- treated CB DCs had similar capacity as prime naïve CD4+ T cells did to produce higher IFN-γ, lower IL-10 production, and CTLA-4 expression compared with their adult counterparts. Conclusion: These results suggested that BCG-treated CB DCs might be semi-mature DCs which polarize naïve T cells into a tolerogenic T cell phenotype in newborns. ©Children's Hospital, Zhejiang University School of Medicine, China and Springer-Verlag Berlin Heidelberg 2010.link_to_subscribed_fulltex