Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo

The adaptive immune system has evolved distinct responses against different pathogens, but the mechanism(s) by which a particular response is initiate d is poorly understood. In this study, we investigated the type of Ag-speci fic CD4(+) Th and CD8(+) T cell responses elicited in vivo, in response to soluble OVA, coinjected with LPS from two different pathogens. We used Esch erichia coli LPS, which signals through Toll-like receptor 4 (TLR4) and LPS from the oral pathogen Porphyromonas gingivalis, which does not appear to require TLR4 for signaling. Coinjections of E. coli LPS + OVA or P. gingiva lis LPS + OVA induced similar clonal expansions of OVA-specific CD4+ and CD 8+ T cells, but strikingly different cytokine profiles. E. coli LPS induced a Th1-like response with abundant IFN-gamma, but little or no IL-4, IL-13, and IL-5. In contrast, P. gingivalis LPS induced Th and T cell responses c haracterized by significant levels of IL-13, IL-5, and IL-10, but lower lev els of IFN-gamma. Consistent with these results, E. coli LPS induced IL-12( p70) in the CD8 alpha (+) dendritic cell (DC) subset, while P. gingivalis L PS did not. Both LPS, however, activated the two DC subsets to up-regulate costimulatory molecules and produce IL-6 and TNF-alpha. Interestingly, thes e LPS appeared to have differences in their ability to signal through TLR4; proliferation of splenocytes and cytokine secretion by splenocytes or DCs from TLR4-deficient C3H/HeJ mice were greatly impaired in response to E. co li LPS, but not P. gingivalis LPS. Therefore, LPS from different bacteria a ctivate DC subsets to produce different cytokines, and induce distinct type s of adaptive immunity in vivo.