Recognition of bacterial polysaccharides by host molecules and development of the immune response Our laboratory studies the interaction of bacterial polysaccharides (PS) with cells of innate immunity. We gathered our aims in two studies to understand the effect of bacterial PSs on innate cells. The first study seeks to determine the effect of PSs on toll like receptor (TLR) mediated cell activation. Our results showed that bacterial PSs alter lipopolysaccharide (LPS) induced cytokine secretion from monocytes and macropages. These results are supported with the observation that encapsulated bacteria induces lower levels of inflammatory cytokines from cells of innate immunity compared to their isogenic unencapsulated counterparts. LPS is a ligand for TLR4 and induces the secretion of inflammatory cytokines (IL-6, TNF-a, IL-12, and IFN-a) from macrophages, monocytes, dentritic cells, and B lymphocytes. These cytokines are shown to modulate acquired immune responses to antigens. We are currently studying the mechanisms of the effect of PSs on TLR mediated activation of innate cells. Delineation of this effect on innate cell activation may help us understand the development of acquired immune response against bacterial PS vaccines and encapsulated bacteria. Our second study addresses the mechanisms of APRIL and BAFF secretion in response to PS immunization. APRIL and BAFF are shown to be important molecules in the development of humoral immune response against bacterial PS antigens. In this project we are seeking to identify the cells that secrete APRIL and BAFF in response to PSs. We are also seeking to understand if there is a difference between infant and adult APRIL/BAFF immunobiology. Since infants are known to be nonresponders to PS vaccines, we would like to investigate if immaturity in APRIL/BAFF biology can be the underlying reason for the lack of response to PS antigens in infants. At the moment commercially available reagents for the detection of APRIL and BAFF molecules do not exist. We are collaborating with researchers from other laboratories to obtain antibodies to be used in immunodetection of APRIL/BAFF in solutions. In parallel, we are running RT-PCR assays to detect APRIL and BAFF mRNA. Our preliminary results indicate that infants do not have an intrinsic immaturity in APRIL/BAFF expression since cord blood cells and adult PBMCs express comparable levels of APRIL/BAFF mRNA in response to IFN-a stimulation. We are now studying the differences in infant and adult cell APRIL/BAFF mRNA levels in response to PS stimulation. We will extend these studies to compare the biological activity of infant and adult APRIL/BAFF molecules on B cells to determine if infant B cells respond to infant APRIL/BAFF as good as adult cells.
