Participation of short chain fatty acids and their receptor (FFAR2) in the immune response to a monoinfection model of Aggregatibacter actinomycetemcomitans

Author(s)

Renan Oliveira Corrêa

• Document type: Master's Dissertation
• Defense date: 2017
• Advisor: Marco Aurélio Ramirez Vinolo

Abstract

Short chain fatty acid (SCFAs), acetate, propionate and butyrate, are end products derived from bacterial metabolism. They are not only an important energetic substrate to the intestinal epithelial cells, but they are also capable of modulating the activation of the immune system, thereby helping to maintain the host homeostasis. One of the main mechanisms associated with the effects of the SCFAs is the activation of G protein-coupled receptors, including the FFAR2, a surface receptor highly expressed on neutrophils. Although it is already known that anaerobic bacteria are capable of producing high amounts of SCFAs at their infectious sites, the effects of this local production are still unclear. Thus, this study aimed to investigate the effects of these SCFAs, locally produced at the infectious sites, in the immune response against the pathogenic bacteria Aggregatibacter actinomycetemcomitans (Aa). For that, we have used a subcutaneous chamber model in C57BL/6 mice to initiate and maintain a monoinfection of Aa inside the organism of the animals. The SCFAs, inoculated together with the bacteria inside of the chamber, did not alter the pattern of leukocytes migration to the infectious site, but they reduced the capacity of the migrating cells to phagocytose and to destroy the bacteria, decreasing, as well, the production of certain cytokynes and chemokynes (TNF-?, IL-10 and Cxcl2) that are essential to orchestrate the subsequent immune response. These effects were not caused by direct actions of the SCFAs in the bacterial growth or their cytotoxic effects on leukocytes. In vitro, we have seen that incubation with SCFAs reduced the phagocytic capacity and the production of TNF-? by human neuthophils. Lastly, we have also demonstrated that the FFAR2 receptor is important for the response to Aa infection, since that in its absence, there was a reduction in the capacity to eliminate this bacterium. Altogether, these results indicate that the production of the SCFAs in the infectious site interferes with neutrophils actions and with that, it can contribute to the start and progression of the infectious disease (AU)

• FAPESP's process: 14/02560-6 - Role of short chain fatty acids and their receptor (GPR43) in the immune response against Aggregatibacter actinomycetemcomitans in a mono-infection model
• Grantee: Renan Oliveira Corrêa
• Support type: Scholarships in Brazil - Master