Folate Receptor Beta Signaling in the Regulation of Macrophage Antimicrobial Immune Response: A Scoping Review

Abstract

<b><i>Introduction:</i></b> Folate, vitamin B9, is a water-soluble vitamin that is essential to cellular proliferation and division. In addition to the reduced folate carrier, eukaryotic cells take up folate through endocytosis mediated by one of two GPI-anchored folate receptors (FRs), FRα or FRβ. Two other isoforms of FR exist, FRγ and FRδ, neither of which support endocytic activities of FR signaling. FRβ is expressed primarily by monocytes and macrophages and highly expressed on activated macrophages. Macrophage expression of FRβ suggests a role for this receptor in modulating function of these immune sentinels, particularly as they engage in inflammatory processes. Despite several studies suggesting that folates can suppress inflammatory responses of macrophages to proinflammatory stimuli, there appears to be a lack of basic research examining the role of FRβ in modulating macrophage responses to microbial sensing. We therefore conducted a scoping review to assess evidence within the published literature addressing the question, “what is known about the extent to which FRβ regulates macrophage responses to sensing, and responding to, microorganisms?”. <b><i>Methods:</i></b> As a strategy for the study selection, we queried articles indexed in the research database PubMed and the search engine Google Scholar (up until August 12, 2023), including combinations of the research words: macrophage, folate receptor beta, <i>FOLR2</i>. <b><i>Results:</i></b> We identified 2 relevant articles out of 153 that are worth discussing here, none of which directly addressed our research question. <b><i>Conclusion:</i></b> There is an unmet need to better define the contribution of FRβ to regulating the macrophage response to microbes.