Metabolic changes induced by complete Freund's adjuvant resemble the features of trained immunity

Abstract Using the mouse model of viral myocarditis, we recently reported that animals immunized with complete Freund’s adjuvant (CFA) conferred complete protection against Coxsackievirus B3 infection. Because that Bacillus Calmette-Guérin (BCG) is a well-known inducer of trained immunity and both CFA and BCG possess similar mycobacterial components, we sought to test the hypothesis that the trained immunity might be the underlying mechanism of CFA-mediated protection against CVB3. By using incomplete Freund’s adjuvant (IFA) as a negative control, we investigated the metabolic profiles by mass spectrometry in bone marrow-derived monocytes and CD11b+ cells sorted from splenocytes using LPS as a secondary stimulus. The analysis revealed elevated levels of lactate, α-ketoglutarate, fumarate, malate, and oxaloacetate in the CFA group as compared with the control or IFA groups. In contrast, S-adenosyl methionine and homoserine levels were high in the IFA group. Overall, our data suggest that the metabolites produced in response to CFA were uniquely different from those of IFA. Whether these profiles correlate with the epigenetic changes are currently being investigated. Supported by grants from NIH (R21, A116673)