The Role of Schistosoma Mansoni Eggs in Protection against Plasmodium Berghei Infected Mice

The co-occurrence of malaria and schistosomiasis is common in tropical regions of the world. Malaria remains a global burden with no vaccine discovered yet. These necessitated the need to look at the immune responses that could be triggered in a coinfection setting. Malaria induces a strong Th1 response while schistosomiasis skews the response to a Th2. This study examined the role of Schistosoma mansoni eggs on malaria disease progression in BALB/c mice infected with Plasmodium berghei. The objectives were to determine the immune correlates to protection. Two groups of mice were used: the experimental and control groups. Experimental were injected with a triple dose of S. mansoni eggs at ten day interval before being challenged with P. berghei while controls were infected with P. berghei only. Five mice from both groups at each time point were euthanized and spleen and serum collected. Mice were euthanized at day 3, 6, 9 and 12 post-challenge with P. berghei. Parasitaemia was monitored daily using Giemsa stained blood smears. Results showed that experimental mice exhibited lower levels of P. berghei parasitaemia (15.52%) as compared to the controls (23.06%). IgG levels were high in the experimental mice compared to controls following stimulation by soluble egg antigen (SEA). Differences in IgG levels between the two study groups were not significant (p>0.05). Levels of IFN- ? and IL-4 were high in the experimental mice than the control group though the difference was not significant (p=0.213). S. mansoni eggs did not induce significant differences in cytokine and IgG levels; nevertheless they contributed to delaying death in the experimental mice by two days by enhancing levels of IgG and IL-4. These findings provide grounds for further studies in non-human primates to better understand the immunomodulatory role of schistosome eggs on malaria progression. Keywords: Schistosoma mansoni, Plasmodium berghe, iSoluble egg Antige

Alterations in preconception, antenatal, and postnatal maternal gut microbiota influence offspring intestinal microbiota and immunity

Maternal microbiota during pregnancy, as well as maternal disease state, may impact offspring gut bacterial colonisation. Here, we explore the impact of maternal antibiotics during gestation and/or nursing on offspring gut microbiota. Further, we investigate the effect of preconception helminth infections on maternal and infant gut microbiota. For maternal antibiotic experiments, dams were fed vancomycin, polymyxin B, or both, in drinking water during gestation, nursing or gestation plus nursing, and their offspring microbiota analysed at 14 days of life, alongside immunity in the spleens. Offspring born to vancomycin treated mothers had significantly higher relative abundance of Proteobacteria and Tenericutes while maternal oral polymyxin B led to significantly lower abundance of Proteobacteria and Deferribacteres in infants. Maternal oral vancomycin led to significant reduction in proportions of infant central memory CD4+ T cells (CD4+CD44hiCD62Lhi) regardless of antibiotic timing. Effector memory CD4+ T cells were significantly lower in pups born to dams treated with polymyxin B while nursing while proportions of central memory CD4 T cells were significantly increased in gestation only or gestation plus nursing pups. In addition, oral vancomycin in dams during nursing resulted in significantly reduced proportions of both total and follicular B cells in offspring born to antibiotic treated dams. Pups born to Vancomycin treated mothers had a significant delay in growth when infected with Respiratory Syncytial Virus (RSV). On the other hand, pups born to mothers treated with Polymyxin B during gestation or gestation plus nursing were susceptible to Nippostrongylus brasiliensis (Nb) infection. In the second study, we infected female BALB/c mice with 500Nb L3 three weeks prior to mating and examined the effect of preconception helminth infection on offspring microbiota and immunity. Preconception Nb infections led to alterations of maternal gut microbiota during pregnancy. In addition, we observed dramatic differences in offspring microbiota in pups born to previously helminth infected dams. Coriobacteriaceae were predominant in pups born to previously Nb infected dams when compared to uninfected dams. Overall, manipulation of maternal microbiota during gestation or lactation profoundly impacts offspring growth, intestinal microbiota and immunity to RSV and helminths

Comparison of non-magnetic and magnetic beads multiplex assay for assessment of Plasmodium falciparum antibodies

Background New reagents have emerged allowing researchers to assess a growing number of vaccine-associated immune parameters. Multiplex immunoassay(s) are emerging as efficient high-throughput assays in malaria serology. Currently, commercial vendors market several bead reagents for cytometric bead assays (CBA) but relative performances are not well published. We have compared two types of bead-based multiplex assays to measure relative antibody levels to malarial antigens. Methods Assays for the measurement of antibodies to five Plasmodium falciparum vaccine candidates using non-magnetic and magnetic fluorescent microspheres were compared for their performances with a Bio-Plex200 instrument. Mean fluorescence intensity (MFI) was determined from individuals from western Kenya and compared to known positive and negative control plasma samples. Results P. falciparum recombinant antigens were successfully coupled to both non-magnetic and magnetic beads in multiplex assays. MFIs between the two bead types were comparable for all antigens tested. Bead recovery was superior with magnetic beads for all antigens. MFI values of stored non-magnetic coupled beads did not differ from freshly coupled beads, though they showed higher levels of bead aggregation. Discussion Magnetic and non-magnetic beads performed similarly in P. falciparum antibody assays. Magnetic beads were more expensive, but had higher bead recovery, were more convenient to use, and provided rapid and easy protocol manipulation. Magnetic beads are a suitable alternative to non-magnetic beads in malarial antibody serology

Pre-conception maternal helminth infection transfers via nursing long-lasting cellular immunity against helminths to offspring

Maternal immune transfer is the most significant source of protection from early-life infection, but whether maternal transfer of immunity by nursing permanently alters offspring immunity is poorly understood. Here, we identify maternal immune imprinting of offspring nursed by mothers who had a pre-conception helminth infection. Nursing of pups by helminth-exposed mothers transferred protective cellular immunity to these offspring against helminth infection. Enhanced control of infection was not dependent on maternal antibody. Protection associated with systemic development of protective type 2 immunity in T helper 2 (TH2) impaired IL-4R-/- offspring. This maternally acquired immunity was maintained into maturity and required transfer (via nursing) to the offspring of maternally derived TH2-competent CD4 T cells. Our data therefore reveal that maternal exposure to a globally prevalent source of infection before pregnancy provides long-term nursing-acquired immune benefits to offspring mediated by maternally derived pathogen-experienced lymphocytes. © 2019 by the Authors

Placental microbial–metabolite profiles and inflammatory mechanisms associated with preterm birth

There is growing emphasis on the potential significance of the placental microbiome and microbiome–metabolite interactions in immune responses and subsequent pregnancy outcome, especially in relation to preterm birth (PTB). This review discusses in detail the pathomechanisms of placental inflammatory responses and the resultant maternal–fetal allograft rejection in both microbial-induced and sterile conditions. It also highlights some potential placental-associated predictive markers of PTB for future investigation. The existence of a placental microbiome remains debatable. Therefore, an overview of our current understanding of the state and role of the placental microbiome (if it exists) and metabolome in human pregnancy is also provided. We critical evaluate the evidence for a placental microbiome, discuss its functional capacity through the elaborated metabolic products and also describe the consequent and more established fetomaternal inflammatory responses that stimulate the pathway to preterm premature rupture of membranes, preterm labour and spontaneous PTB

Metadata

Metadata of breastmilk microbiota collected day 14 postpartum<div><br></div

Pups OTU table

OTU table of pup gut microbiot

Metadata Genital tract

Metadata of genital tract microbiota<div><br></div

OTU table Pups only Combined Expts

Combining pups stool microbiota across experiment to control cage effec

Metadata Breastmilk

Metadata of breastmilk collected day 4 postpartum<div><br></div