Project description:Healthy Kenyan children with (n=10) or without (n=14) a previous history of complicated Plasmodium falciparum infection had aliquots of their whole-blood cultured ex-vivo and either mock infected or infected with Plasmodium falciparum (A4 strain) for 5 (n=24) and 9 hours (n=11). A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Time: lenght of co-culture Infection: whole-blood cells cultured ex-vivo in the presence of either uninfected red blood cells or red blood cells infected with Plasmodium falciparum Disease State: Healthy individuals with (PrevHxMal) or without (NoHxMal) previous exposure to complicated Plasmodium falciparum infection clinical_history_design
Project description:Healthy Kenyan children with (n=10) or without (n=14) a previous history of complicated Plasmodium falciparum infection had aliquots of their whole-blood cultured ex-vivo and either mock infected or infected with Plasmodium falciparum (A4 strain) for 5 (n=24) and 9 hours (n=11). A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Time: lenght of co-culture Infection: whole-blood cells cultured ex-vivo in the presence of either uninfected red blood cells or red blood cells infected with Plasmodium falciparum Disease State: Healthy individuals with (PrevHxMal) or without (NoHxMal) previous exposure to complicated Plasmodium falciparum infection
Project description:Gene expression data from whole-blood collected from Kenyan children with Plasmodium falciparum malaria infection at acute hospital admission (n=15) and at convalescence (n=9). A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Disease State: with Plasmodium falciparum malaria infection at acute hospital admission and at convalescence clinical_history_design
Project description:Gene expression data from whole-blood collected from Kenyan children with Plasmodium falciparum malaria infection at acute hospital admission (n=15) and at convalescence (n=9). A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Disease State: with Plasmodium falciparum malaria infection at acute hospital admission and at convalescence
Project description:Gene expression data from Vietnamese subjects admitted to hospital with acute uncomplicated (n=6) or complicated (n=6) Plasmodium falciparum malaria infection had whole-blood samples collected at admission, 1 week later and 1 month later. Groups of assays that are related as part of a time series. Disease State: patient with complicated or uncomplicated Plasmodium falciparum malaria infection or Healthy control time_series_design
Project description:Gene expression data from Vietnamese subjects admitted to hospital with acute uncomplicated (n=6) or complicated (n=6) Plasmodium falciparum malaria infection had whole-blood samples collected at admission, 1 week later and 1 month later. Groups of assays that are related as part of a time series. Disease State: patient with complicated or uncomplicated Plasmodium falciparum malaria infection or Healthy control
Project description:Gene expression data from whole-blood collected from healthy Vietnamese subjects (n=8) or from patients admitted to hospital with acute uncomplicated (n=9) or complicated (n=20) Plasmodium falciparum malaria infection. A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Disease State: patient with complicated or uncomplicated Plasmodium falciparum malaria infection or Healthy control clinical_history_design
Project description:Gene expression data from whole-blood collected from healthy Vietnamese subjects (n=8) or from patients admitted to hospital with acute uncomplicated (n=9) or complicated (n=20) Plasmodium falciparum malaria infection. A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Disease State: patient with complicated or uncomplicated Plasmodium falciparum malaria infection or Healthy control
Project description:In malaria infection, Plasmodium spp. parasites accumulate in the bone marrow near sites of erythroid development. While it has been observed that Plasmodium falciparum infection of late-stage erythroblasts can delay terminal erythroid differentiation and enucleation, the mechanism(s) underlying this phenomenon are unknown. Here, we apply RNA-seq after fluorescence-activated cell sorting (FACS) of infected erythroblasts to identify transcriptional responses to direct and indirect interaction with P. falciparum.
Project description:The mosquito Anopheles gambiae uses its innate immune system to control bacterial and Plasmodium infection of its midgut tissue. The activation of potent IMD pathway-mediated anti-Plasmodium falciparum defenses is dependent on the presence of the midgut microbiota, which activate this defense system upon parasite infection through a peptidoglycan recognition protein, PGRPLC. We employed transcriptomic and reverse genetic analyses to compare the P. falciparum infection-responsive transcriptomes of septic and aseptic mosquitoes and to determine whether bacteria-independent anti-Plasmodium defenses exist. To examine the impact of P. falciparum infection on the mosquito midgut and carcass transcriptomes in the presence or absence of midgut bacteria, we used A. gambiae whole genome microarrays to compare the mRNA abundance of P. falciparum-infected and -naïve mosquitoes of antibiotic- and non-antibiotic treated cohorts. P. falciparum infection induced changes in the abundance of as many as 2,183 and 2,429 transcripts in whole mosquitoes belonging to a variety of functional groups in aseptic and septic mosquitoes. Ultimately, we were interested in identifying the genes involved in bacteria-independent anti-Plasmodium responses, and therefore we focused on transcripts displaying increased abundance in the parasite-infected aseptic midguts, placing a particular emphasis on those with predicted immune functions. Because of the central role of serine protease cascades in regulating insect immune defenses, we focused the remainder of our analysis on a clip-domain serine protease C2 (CLIPC2, AGAP004317) and a serine protease inhibitor 7 (SRPN7, AGAP007693) that were specifically upregulated in the parasite-infected, aseptic mosquito midgut. We showed that SRPN7 negatively and CLIPC2 positively regulate the anti-Plasmodium defense, independently of the midgut-associated bacteria. Co-silencing assays suggested that these two genes may function together in a signaling cascade. Neither gene was regulated, nor modulated, by infection with the rodent malaria parasite Plasmodium berghei, suggesting that SRPN7 and CLIPC2 are components of a defense system with preferential activity towards P. falciparum. Further analysis using RNA interference determined that these genes do not regulate the anti-Plasmodium defense mediated by the IMD pathway, and both factors act as agonists of the endogenous midgut microbiota, further demonstrating the lack of functional relatedness between these genes and the bacteria-dependent activation of the IMD pathway. This is the first study confirming the existence of a bacteria-independent, anti-P. falciparum defense. Aseptic and septic midguts and carcasses from P. falciparum-infected A. gambiae vs aseptic and septic midguts and carcasses from uninfected, blood-fed A. gambiae. 3 biological replicates and 1 pseudo-replicate per each array.