Leishmania major:: Recruitment of Gr-1+ cells into draining lymph nodes during infection is important for early IL-12 and IFNγ production

The production of interleukin-12 and interferon-gamma is a key event for controlling leishmaniasis. Here. we tested the hypothesis that after murine infection with Leishmania major, cell migration into draining lymph nodes is crucial for early production of those cytokines. We showed that inflammatory cells carrying the marker of recently migrated cells, the Gr-1 antigen, including polymorphonuclear and mononuclear cells. migrate rapidly into the site of promastigote infection and, subsequently. into draining lymph nodes. Treatment with RB6-8C5 monoclonal antibody reduced local inflammation and migration of Gr-1+ cells into the draining lymph nodes. This reduction was associated with a decrease of interleukin-12 production by draining lymph node cells from BALB/c mice but not c57BL/6 mice. Additionally. interferon-gamma was also reduced in both mouse strains after depletion of Gr-1+ cells, suggesting that these cells are important for early interleukin-12 and interferon-gamma production. Our findings suggest that recently migrated myeloid cells, more than resident cells, are the major source of the early IL-12 production after L major infection. (c) 2008 Elsevier Inc. All rights reserved.