A live Leishmania major vaccine containing CpG motifs induces the de novo generation of Th17 cells in C57BL/6 mice.
Cutaneous leishmaniasis produces open sores that lead to scarring and disfiguration. We have reported that vaccination of C57BL/6 mice with live Leishmania major plus CpG DNA (Lm/CpG) prevents lesion development and provides long-term immunity. Our current study aims to characterize the components of the adaptive immune response that are unique to Lm/CpG. We find that this vaccine enhances the proliferation of CD4(+) Th17 cells, which contrasts with the highly polarized Th1 response caused by L. major alone; the Th17 response is dependent upon release of vaccine-induced IL-6. Neutralization of IFN-gamma and, in particular, IL-17 caused increased parasite burdens in Lm/CpG-vaccinated mice. IL-17R-deficient Lm/CpG-vaccinated mice develop lesions, and display decreased IL-17 and IFN-gamma, despite normal IL-12, production. Neutrophil accumulation is also decreased in the IL-17R-deficient Lm/CpG-vaccinated mice but Treg numbers are augmented. Our data demonstrate that activation of immune cells through CpG DNA, in the presence of live L. major, causes the specific induction of Th17 cells, which enhances the development of a protective cellular immunity against the parasite. Our study also demonstrates that vaccines combining live pathogens with immunomodulatory molecules may strikingly modify the natural immune response to infection in an alternative manner to that induced by killed or subunit vaccines.
Wu
Wenhui
W
Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Huang
Lu
L
Mendez
Susana
S
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D018899:CpG Islands / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D054332:Leishmaniasis Vaccines; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000235:genetics; D012867:Skin / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014611:Vaccination
D019138:Antibodies, Blocking; D020381:Interleukin-17; D015850:Interleukin-6; D054332:Leishmaniasis Vaccines; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma