Inoculation of killed Leishmania major into immune mice rapidly disrupts immunity to a secondary challenge via IL-10-mediated process

Ifeoma Okwor, Dong Liu, Stephen M. Beverley, Jude E. Uzonna

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Recovery from natural or experimental Leishmania major infection, the causative agent of cutaneous leishmaniasis, results in development of durable immunity in mice and humans that is manifested as rapid control of parasite replication and resolution of cutaneous lesion after secondary challenge. This form of "infection-induced" immunity is thought to occur naturally in endemic areas and is generally considered the gold standard for any effective vaccine against cutaneous leishmaniasis. To determine factors that might heighten or abrogate infection-induced immunity, we investigated the impact of inoculating dead antigen in the form of killed Leishmania parasites to healed mice. We show that inoculation of killed parasites into mice that resolved their primary virulent L. major infection results in rapid and relatively sustained loss of infection-induced immunity. This loss of immunity was not due to the inability of killed parasites to induce inflammatory responses (such as delayed type hypersensitivity), but it was related to their failure to induce robust IFN-γ response. Furthermore, inoculation of killed Leishmania parasites into healed mice led to rapid expansion of IL-10-producing CD4 +CD25+Foxp3+ T cells in lymph nodes draining the primary infection site. Treatment with anti-CD25 or anti-IL-10R mAb abolished killed parasite-induced loss of immunity. Our study suggests that vaccination with killed parasites could predispose naturally immune individuals to become susceptible to new infections and/or disease reactivation. This may account for the lack of efficacy of such vaccines in field trials in endemic regions. These findings have important implications for vaccine design and vaccination strategies against human cutaneous leishmaniasis.

Original languageEnglish
Pages (from-to)13951-13956
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number33
DOIs
StatePublished - Aug 18 2009

Keywords

  • Cytokines
  • Memory
  • Parasitic-protozoa
  • Regulatory T cells
  • Vaccination

Fingerprint

Dive into the research topics of 'Inoculation of killed Leishmania major into immune mice rapidly disrupts immunity to a secondary challenge via IL-10-mediated process'. Together they form a unique fingerprint.

Cite this