Malhotra, I. et al. (2009) Can Prenatal Malaria Exposure Produce an Immune Tolerant Phenotype?: A Prospective Birth Cohort Study in Kenya. PLoS Medicine. Volume 6(7): e1000116 Presented by: Isabel & Rachelle
ExperimentalApproach: • Exposed sensitized was demonstrated by IFN, IL-2, IL-13 & IL-5 production by cord blood mononuclear cells (CBMCs) to malaria blood stage antigens. • Exposed not sensitized (Putatively tolerant) newborns had to have their mother’s plasmodium falciparum [Pf]+ and no CBMC production. • Not exposed had to be negative for both Pf and CBMC
Main Finding: • Offspring of women with malaria at delivery have evidence for impaired acquisition of malaria-specific antibodies, as well as reduced levels of functional antibodies that inhibit invasion of erythrocytes by the membrane-anchored MSP1, a protein required for entry of the parasite into red blood cells. • Based on light microscopy or PCR diagnosis it was shown that exposed not sensitized children had increase IL-10 production & partial reversal of malaria antigen-specific hyporesponsiveness with IL2 + IL15, indicating immune tolerance. • Exposed not sensitized children showed 2 to 3-fold lower frequency of malaria antigen-driven IFN or IL-2 production and higher IL-10 release at six month follow-ups. • Malaria blood stage-specific IgG antibody levels were similar among the three groups.
Critique • Fig5: No explanation is offered as to why they seemingly tested the Th 2 type response twice (the IL 10 and IL5/IL 13) • Researchers used controls for most experiments and reported set definitions for quantifying data; however, they referenced a lot of unpublished data and even personal communication.
Discussion: • Cytokines down grades immune response, note that IL- 2 and IL-10 have an opposite response in graph A and B because IL- 10 increases the immune response against malaria. • There is a recommendation for pregnant women to take malaria chemoprophylaxis which prevents infection during pregnancy. • A critique should be that they didn’t look for any clinical symptoms instead they only looked for the presence of the organism, which prevented the observation of whether the tolerance level helped prevent symptoms when the organism is present.