RESUMO
Several reports have shown that cutaneous leishmaniasis lesions are painless, suggesting that Leishmania infection interferes with pain perception. Comparisons of inflammation-induced hyperalgesia between BALB/c and C57BL/6 mice have been little explored in the literature, and comparative data regarding nociception in leishmaniasis are non-existent. In susceptible BALB/c mice and resistant C57BL/6 mice that were intradermally inoculated with a low dose of Leishmania major in the ear, we investigated the variation in nociception over a 12-wk period post-infection and this variation's association with the structure of nerve fibres and the presence of endogenous cytokines that are classically considered hyper- or hypo-nociceptive. Infected BALB/c mice presented susceptibility and severe lesions. Infected C57BL/6 mice exhibited resistance and healing lesions. The immune response involved pro- and anti-inflammatory cytokine secretion, respectively. The infection-induced hypoalgesia in BALB/c mice after wks 9 was accompanied by decreased levels of IL-6 and IL-10 in ear tissue with intact nerves. C57BL/6 mice showed short-lived hyperalgesia in wks 2, which was related to increased local levels of IL-6, KC/CXCL-1, TNF-α and IL-10 and a decrease in nerve density. The increase in pro-inflammatory cytokine IL-6, KC/CXCL-1 and TNF-α levels during hyperalgesia suggested a role for these mediators in afferent nerve sensitisation, which was secondary to the inflammatory damage of nerve fibres stained by PGP 9.5. In contrast, the mechanisms of hypoalgesia may include the downregulation of cytokines, the preservation of the structure of nerve endings, and as yet uninvestigated unidentified differences in neurotransmitter release or a direct role of the parasites in the context of the progressive and permissive inflammatory response of BALB/c mice.
Assuntos
Citocinas/análise , Orelha Externa/parasitologia , Leishmania major/imunologia , Leishmaniose Cutânea/fisiopatologia , Nociceptividade/fisiologia , Animais , Citocinas/metabolismo , Regulação para Baixo , Orelha Externa/imunologia , Orelha Externa/inervação , Feminino , Imuno-Histoquímica , Leishmania major/patogenicidade , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dor Nociceptiva/etiologia , Dor Nociceptiva/imunologia , Dor Nociceptiva/fisiopatologia , Limiar da Dor/fisiologia , Ubiquitina Tiolesterase/análiseRESUMO
This study evaluated two vaccine candidates for their effectiveness in protecting BALB/c mice against Leishmania chagasi infection. These immunogenic preparations were composed of Leishmania amazonensis or Leishmania braziliensis antigenic extracts in association with saponin adjuvant. Mice were given three subcutaneous doses of one of these vaccine candidates weekly for three weeks and four weeks later challenged with promastigotes of L. chagasi by intravenous injection. We observed that both vaccine candidates induced a significant reduction in the parasite load of the liver, while the L. amazonensis antigenic extract also stimulated a reduction in spleen parasite load. This protection was associated with a suppression of both interleukin (IL)-10 and IL-4 cytokines by spleen cells in response to L. chagasi antigen. No change was detected in the production of IFN-γ. Our data show that these immunogenic preparations reduce the type 2 immune response leading to the control of parasite replication.
Assuntos
Antígenos de Protozoários/imunologia , Interleucina-10/biossíntese , Interleucina-4/biossíntese , Vacinas contra Leishmaniose/imunologia , Leishmaniose Cutânea/imunologia , Animais , Antígenos de Protozoários/administração & dosagem , Feminino , Interleucina-10/imunologia , Interleucina-4/imunologia , Leishmania braziliensis/imunologia , Leishmania infantum/imunologia , Leishmania mexicana/imunologia , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/prevenção & controle , Fígado/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Saponinas/administração & dosagem , Saponinas/imunologia , Baço/parasitologiaRESUMO
This study evaluated two vaccine candidates for their effectiveness in protecting BALB/c mice against Leishmania chagasiinfection. These immunogenic preparations were composed of Leishmania amazonensisor Leishmania braziliensisantigenic extracts in association with saponin adjuvant. Mice were given three subcutaneous doses of one of these vaccine candidates weekly for three weeks and four weeks later challenged with promastigotes of L. chagasiby intravenous injection. We observed that both vaccine candidates induced a significant reduction in the parasite load of the liver, while the L. amazonensisantigenic extract also stimulated a reduction in spleen parasite load. This protection was associated with a suppression of both interleukin (IL)-10 and IL-4 cytokines by spleen cells in response to L. chagasiantigen. No change was detected in the production of IFN-γ. Our data show that these immunogenic preparations reduce the type 2 immune response leading to the control of parasite replication.
Assuntos
Animais , Feminino , Camundongos , Antígenos de Protozoários/imunologia , /biossíntese , /biossíntese , Vacinas contra Leishmaniose/imunologia , Leishmaniose Cutânea/imunologia , Antígenos de Protozoários , /imunologia , /imunologia , Leishmania braziliensis/imunologia , Leishmania infantum/imunologia , Leishmania mexicana/imunologia , Leishmaniose Cutânea , Leishmaniose Cutânea , Fígado , Camundongos Endogâmicos BALB C , Saponinas , Saponinas/imunologia , BaçoRESUMO
Acute visceral leishmaniasis is a progressive disease caused by Leishmania chagasi in South America. The acquisition of immunity following infection suggests that vaccination is a feasible approach to protect against this disease. Since Leishmania homologue of receptors for activated C kinase (LACK) antigen is of particular interest as a vaccine candidate because of the prominent role it plays in the pathogenesis of experimental Leishmania major infection, we evaluated the potential of a p36(LACK) DNA vaccine in protecting BALB/c mice challenged with L. chagasi. In this study, mice received intramuscular (i.m.) or subcutaneous (s.c.) doses of LACK DNA vaccine. We evaluated the production of vaccine-induced cytokines and whether this immunization was able to reduce parasite load in liver and spleen. We detected a significant production of interferon gamma by splenocytes from i.m. vaccinated mice in response to L. chagasi antigen and to rLACK protein. However, we did not observe a reduction in parasite load neither in liver nor in the spleen of vaccinated animals. The lack of protection observed may be explained by a significant production of IL-10 induced by the vaccine.