Hyperglycemia alters the inflammatory response of bone marrow derived macrophages

Abstract

Nod-Like Receptors (NLRs) are a type of immune receptor working to incite or dampen inflammation by means of downstream cytokine release. NLRP12 has been implicated in being a negative regulator of inflammatory responses by working in contrast to more well studied NLRs such as NLRP3. In the literature, the function of NLRP12 under normal glucose conditions is well documented. However, its ability to respond to pathogens under elevated levels of glucose, for example in diabetic conditions in vivo is not well characterized. Utilizing bone marrow derived macrophages cultured under varying glucose concentrations, this study examined the ability of NLRP12 to respond to antigen, utilizing a variety of ligands and bacterial strains. After exposure, the responses of both wild-type and NLRP12 deficient macrophages were evaluated by quantifying levels of secreted IL-1β and IFNγ as a measure of an inflammatory response using ELISA. The results of this study validate known scientific literature regarding NLRP12 as a negative regulator of inflammation, and additionally reveal that bone marrow derived macrophages cytokine response to Salmonella enterica is impaired under hyperglycemia, which could improve current understanding of in vivo diabetic immunity.