Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract

Introduction The attenuation of BCG has led to the loss of not only immunogenic proteins but also lipid antigens. Methods Thus, we compared the macrophage and T-cell responses to nonpolar lipid extracts harvested from BCG and Mycobacterium tuberculosis ( Mtb ) to better understand the role of BCG lipids in the already known diminished responses of the vaccine strain. Results Relative to Mtb, nonpolar lipid extract from BCG presented a reduced capacity to trigger the expression of the genes encoding TNF, IL-1b, IL-6 and IL-10 in RAW 264.7 macrophages. Immunophenotyping of PBMCs isolated from healthy individuals revealed that lipids from both BCG and Mtb were able to induce an increased frequency of CD4 + and CD8 + T cells, but only the lipid extract from Mtb enhanced the frequency of CD4 - CD8 - double-negative, γσ + , CD4 + HLA-DR + , and γσ + HLA-DR + T cells relative to the nonstimulated control. Interestingly, only the Mtb lipid extract was able to increase the frequency of CD4 + memory (CD45RO + ) T cells, whereas the BCG lipid extract induced a diminished frequency of CD4 + central memory (CD45RO + CCR7 - ) T cells after 48 h of culture compared to Mtb . Discussion These findings show that the nonpolar lipids of the BCG bacilli presented diminished ability to trigger both proinflammatory and memory responses and suggest a potential use of Mtb lipids as adjuvants to increase the BCG vaccine efficacy.