BCG-treated M2-macrophages enhance IFN-γ production of T cells (P3348)

Abstract

Abstract M1- and M2-polarized Macrophage (MΦ) subtypes differentially regulate anti-mycobacterial defense. To examine their roles in human infection, we compared the gene expression profile of M1- vs. M2-MΦ to the expression profile of lesional skin from patients with restricted (tuberculoid, T-lep) vs. disseminated (lepromatous, L-lep) leprosy (a mycobacterial skin infection). Rank-Rank Hypergeometric Overlap (RRHO) is a novel algorithm for comparing full gene expression profiles from two independent microarray experiments that generates the most statistically significant overlapping gene list without requiring strict p-value/fold change cutoffs. RRHO analysis showed significant overlap of genes between M2-MΦ and L-lep lesions (n = 1559, max log hypergeometric p-value = 196), indicating a role for M2-MΦ in immune unresponsiveness. Bacillus Calmette-Guerin (BCG) is given to protect household contacts against leprosy. We hypothesized that BCG treatment may affect the function of M2-MΦ and investigated its effects in vitro. We found that BCG-treated M2-MΦ secreted less IL-10 (p < 0.05), with no effect on IL-12p40, compared to untreated M2-MΦ. In addition, BCG-treated M2-MΦ increased the frequency of IFN-γ producing cells in an antigen non-specific manner (p < 0.05), suggesting an adjuvant effect of BCG. Our data indicates M2-MΦ can be reprogrammed by BCG, resulting in increased IFN-γ production to enhance anti-mycobacterial immunity.