Aspectos imunológicos relacionados à resistência e suscetibilidade na coinfecção experimental murina de Leishmania major com Rhipicephalus sanguineus ou Ascaris lumbricoides

Abstract

Dogs are considered the main domestic reservoirs of visceral leishmaniasis in Brazil and many regions of the world. In nature, a wide range of coinfections may take place in dogs, especially those caused by brown ticks and worms. Ticks saliva has many properties aiming the vector to circumvent the clothing, inflammatory and perception mechanisms of the host. Worms, usually drive the immune response to a TH2 profile which is beneficial to Leishmania parasites. However, the role of the immunomodulation driven by ticks or worms in the outcome of leishmaniasis is poorly known and is still a missing step of the host-parasite interface. Mice (C57BL/6 and BALB/c) were previously infested once by two adult females of Rhipicephalus sanguineus on the dorso-thoracic skin, for 7 to 10 days and infected with 105 metacyclic promastigotes of Leishmania major in the left hind paw as well as a non-infested group. As a control group for some experiments, mice infested by R. sanguineus were inoculated in the footpad with sterile PBS. Footpad thickness was monitored weekly. Parasitism and immunologic parameters were measured at five and eight weeks post infection. The titers of anti-Leishmania antibodies and IL-10 were measured in sera by ELISA and the parasite load in the skin and spleen was measured by qPCR. BALB/c mice were previously infected thrice with 2000 embrionated eggs of Ascaris lumbricoides and then infected with L. major as described before. Infestation with R. sanguineus promoted a minor increase in the thickness of the infected footpad when compared to non-infested mice. However, the parasite load in the paw and spleen was slightly higher in infested groups. Moreover, no difference in footpad swelling was observed in BALB/c mice, but the parasite load in the footpad was slightly higher in the infested group. Interestingly, titers of anti-Leishmania IgG1 and IgG2 antibodies were lower in infested mice eight weeks after the end of infestation. No differences were sought in mice infected with A. lumbricoides, when compared with their control. Moreover, the role of eosinophils were evaluated during the infection of Leishmania using mice lacking these cells. Mice depleted of eosinophils showed a worst development of the disease due to enhanced numbers of metastatic lesions in the skin and reduced survival after challenge. Our data strongly suggests that ticks may affect the immunity and the course of the disease in co-infected mice harboring Leishmania major.