dos Santos Milla Schmaltz Tatico, Vaz Cardoso Ludimila Paula, Nascimento Gustavo Rios, Lino Ruy de Sousa, Dorta Miriam Leandro, de Oliveira Milton Adriano Pelli, Ribeiro-Dias Fátima
Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiás, Brazil.
Exp Parasitol. 2008 Jul;119(3):403-10. doi: 10.1016/j.exppara.2008.04.011. Epub 2008 May 22.
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.
白细胞介素-12和干扰素-γ的产生是控制利什曼病的关键事件。在此,我们验证了以下假说:小鼠感染硕大利什曼原虫后,细胞迁移至引流淋巴结对于这些细胞因子的早期产生至关重要。我们发现,携带近期迁移细胞标志物Gr-1抗原的炎性细胞,包括多形核细胞和单核细胞,迅速迁移至前鞭毛体感染部位,随后进入引流淋巴结。用RB6-8C5单克隆抗体处理可减轻局部炎症,并减少Gr-1+细胞向引流淋巴结的迁移。这种减少与BALB/c小鼠而非C57BL/6小鼠引流淋巴结细胞产生白细胞介素-12的减少有关。此外,在Gr-1+细胞耗竭后,两种小鼠品系中的干扰素-γ也减少,表明这些细胞对于早期白细胞介素-12和干扰素-γ的产生很重要。我们的研究结果表明,近期迁移的髓样细胞而非驻留细胞是硕大利什曼原虫感染后早期白细胞介素-12产生的主要来源。