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 () 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 were able to induce an increased frequency of CD4 and CD8 T cells, but only the lipid extract from enhanced the frequency of CD4CD8double-negative, γσ, CD4HLA-DR, and γσHLA-DR T cells relative to the nonstimulated control. Interestingly, only the 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 (CD45ROCCR7) T cells after 48 h of culture compared to .

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 lipids as adjuvants to increase the BCG vaccine efficacy.