Early farm exposure, including prenatal exposure, is associated with increased mRNA expression of innate immune receptors (TLR2, TLR4, CD14) in peripheral blood mononuclear cells (PBMC). Moreover, epidemiologic studies from multiple continents have found rural farming environments are protective for development of allergic diseases, with a proposed mechanism of skewing toward proinflammatory cytokine responses.
One potential explanation for these findings is that pre- and post-natal stimulation of the innate immune system is necessary for optimal immune maturation. Cross-sectional studies on cord blood of term newborns found both pre- and post-natal environmental exposures are significantly associated with unique patterns of immunologic responses. Specifically, the immune response of infants born into farming environments is associated with increased production of proinflammatory cytokines determined from in vitro culture supernatants after culture with TLR agonists. We have unpublished data showing that Wisconsin farm children in the Marshfield Epidemiology Research Area (MESA) are at significantly lower risk for developing allergic disease and clinically significant respiratory viral illnesses. To date, an immunologic profile that allows protection from clinically significant illnesses has not been defined nor has the TLR-mediated cytokine response been characterized at the cellular level in infants from farming environments.
Our large NIH grant is in its third year of funding. We have reached 75% of our enrollment goal. We have submitted separate proposals to fund the microbiome analysis (pending) and will submit competitive renewal to the NIH to continue to follow this important and unique birth cohort.