Mechanisms
CETP-expressing mice heal cutaneous leishmaniasis lesions faster, shifting macrophages toward a healing M2 phenotype (Front Immunol 2024)
Original title: The impact of cholesteryl ester transfer protein on the progression of cutaneous leishmaniasis
A study infected C57BL6/J mice transgenic for human CETP, and non-expressing wild-type littermates, with Leishmania (L.) amazonensis in the footpad and monitored lesion progression for 12 weeks. Lesions grew from week 3 in both groups but shrank from week 10 onward in CETP-expressing mice compared with wild-type, alongside reduced parasite burden, fewer CD68+ cells and more CD163+ and CD206+ cells, characteristic of healing-associated M2 macrophages, plus fewer ARG1+ and more iNOS+ cells. By 12 weeks, CETP-expressing mice had higher VLDL-fraction triglycerides and lower CD36 receptor expression, which correlated with healing and reduced parasitism. In vitro, CETP-expressing bone-marrow-derived macrophages showed lower parasite load and reduced arginase activity alongside increased nitric oxide production. The authors conclude CETP presence aids resolution of cutaneous leishmaniasis by modulating the inflammatory and healing response, a preclinical infectious-disease finding outside cardiovascular medicine.
Original abstract
Introduction: Pathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions.
Methods: We evaluated the impact of the presence of CETP on infection by Leishmania (L.) amazonensis in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice. The progression of the lesion after infection in the footpad was monitored for 12 weeks. Two groups of animals were formed to collect the plantar pad in the 4th and 12th week post-infection.
Results: The lesion increased from the 3rd week onwards, in both groups, with a gradual decrease from the 10th week onwards in the CETP group compared to the WT group, showing a reduction in parasitism and an improvement in the healing process, a reduction in CD68+ cells, and an increase in CD163+ and CD206, characterizing a population of M2 macrophages. A reduction in ARG1+ cells and an increase in INOS+ cells were observed. During infection, the LP profile showed an increase in triglycerides in the VLDL fraction in the CETP group at 12 weeks. Gene expression revealed a decrease in the CD36 receptor in the CETP group at 12 weeks, correlating with healing and parasite reduction. In vitro, macrophages derived from bone marrow cells from CETP mice showed lower parasite load at 48 h and, a reduction in arginase activity at 4 h accompanied by increased NO production at 4 and 24 h compared to WT macrophages, corroborating the in vivo findings.
Discussion: The data indicate that the presence of CETP plays an important role in resolving Leishmania (L.) amazonensis infection, reducing parasitism, and modulating the inflammatory response in controlling infection and tissue repair.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.