Romão P R T, Da Costa Santiago H, Ramos C D L, De Oliveira C F E, Monteiro M C, De Queiroz Cunha F, Vieira L Q
Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Parasite Immunol. 2009 Mar;31(3):140-6. doi: 10.1111/j.1365-3024.2008.01084.x.
Leishmaniasis causes high morbidity and mortality in tropical and subtropical areas. Mast cells can be activated by Leishmania or Leishmania products in vitro and in vivo. Several innate immunity mediators, including some released by mast cells, play roles in the outcome of the disease. In this study, we examined whether pharmacological inactivation of mast cells before infection with L. major interferes with the progressive disease in BALB/c mice. The results show that, when mast cells are degranulated before challenge with L. major, susceptible mice become more resistant to infection, as measured by decrease of lesion size and lower parasite loads. Mast cell degranulation reduced IL-4 production. Moreover, mast cells degranulation enhanced mRNA expression for IFN-gamma, inducible nitric oxide, CCL2 and CCL5 in response to infection. Mast cell degranulation also decreased parasite loads in IL-4 KO animals, indicating that mediators other than IL-4 are involved in susceptibility in vivo. Taken together, our results disclose a role for mast cells in the induction of susceptibility to infection. This work contributes to a better understanding of the role of mast cells in Leishmania infection, and suggests a new field of study for strategies to contain the parasite, restricting its dissemination.
利什曼病在热带和亚热带地区导致高发病率和死亡率。肥大细胞可在体外和体内被利什曼原虫或其产物激活。包括肥大细胞释放的一些物质在内的多种固有免疫介质在疾病的转归中发挥作用。在本研究中，我们检测了在感染硕大利什曼原虫之前对肥大细胞进行药理学失活是否会干扰BALB/c小鼠的进行性疾病。结果表明，当在感染硕大利什曼原虫之前使肥大细胞脱颗粒时，通过病变大小的减小和较低的寄生虫载量来衡量，易感小鼠对感染的抵抗力增强。肥大细胞脱颗粒减少了白细胞介素-4的产生。此外，肥大细胞脱颗粒增强了感染后干扰素-γ、诱导型一氧化氮、趋化因子配体2和趋化因子配体5的mRNA表达。肥大细胞脱颗粒也降低了白细胞介素-4基因敲除动物的寄生虫载量，表明白细胞介素-4以外的介质也参与了体内易感性。综上所述，我们的结果揭示了肥大细胞在诱导感染易感性中的作用。这项工作有助于更好地理解肥大细胞在利什曼原虫感染中的作用，并为控制寄生虫、限制其传播的策略提出了一个新的研究领域。
