dc.description.abstract | Streptococcus suis (S. suis) is a bacterium that can cause severe illness in both pigs and humans. Currently, treatment of S. suis infection relies on the use of antibiotics. With increasing concerns regarding antibiotic resistance, there is a clear need for alternative treatments. Despite many attempts, vaccination of pigs against this pathogen has not proven effective.
Cathelicidins are peptides that are part of the innate immune system with immunomodulatory properties, making them promising vaccine adjuvants. The porcine cathelicidins PR-39 and PMAP-23 were selected for this study, in addition to a well-documented chicken cathelicidin (chCATH-2). In combination with providing more general knowledge regarding the porcine immune system, this study aimed to investigate whether cathelicidins could be of use as immune modulators of porcine dendritic cells.
Using flow cytometry and cytokine level readouts of porcine bone marrow derived dendritic cells, the effect of S. suis isolate S10 (both encapsulated and non-encapsulated), LPS, and host defense peptides on dendritic cell surface markers was analyzed. chCATH-2 dose-dependently lowered the immune response triggered by S. suis, its non-encapsulated mutant, and LPS, whereas PMAP-23 and PR-39 did not. In contrast, PR-39 increased IL-1ß concentrations in a dose-dependent manner.
Phagocytosis assays using fluorescent S. suis revealed that non-encapsulated S. suis could be taken up by dendritic cells. The capsule of S. suis, however, blocked phagocytosis and the investigated cathelicidins did not increase this uptake. Preliminary co-cultures, using dendritic cells and CD4+ T cells, indicated that chCATH-2 boosts the activation of T helper cells. Together with their antimicrobial properties, these peptides form a promising alternative to antibiotics, either as vaccine adjuvants or immune modulatory drugs. | |