| Autor: |
Avendaño-Rangel F; Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, Brazil.; Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40170-110, BA, Brazil., Agra-Duarte G; Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, Brazil., Borba PB; Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, Brazil., Moitinho V; Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, Brazil., Avila LT; Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, Brazil., da Silva LO; Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, Brazil., Viana SM; Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, Brazil., Sharma R; Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, Brazil., Gannavaram S; Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD 20993, USA., Nakhasi HL; Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD 20993, USA., de Oliveira CI; Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, Brazil.; Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40170-110, BA, Brazil.; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador 40296-710, BA, Brazil. |
| Abstrakt: |
Immunization with various Leishmania species lacking centrin induces robust immunity against a homologous and heterologous virulent challenge, making centrin mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-binding cytoskeletal protein involved in centrosome duplication in higher eukaryotes and Leishmania spp. lacking centrin are unable to replicate in vivo and are non-pathogenic. We developed a centrin -deficient Leishmania braziliensis ( LbCen -/- ) cell line and confirmed its impaired survival following phagocytosis by macrophages. Upon experimental inoculation into BALB/c mice, LbCen -/- failed to induce lesions and parasites were rapidly eliminated. The immune response following inoculation with LbCen -/- was characterized by a mixed IFN-γ, IL-4, and IL-10 response and did not confer protection against L. braziliensis infection, distinct from L. major , L. donovani , and L mexicana centrin-deficient mutants. A prime-boost strategy also did not lead to a protective immune response against homologous challenge. On the contrary, immunization with centrin -deficient L. donovani ( LdonCen -/- ) cross-protected against L. braziliensis challenge, illustrating the ability of LdonCen -/- to induce the Th1-dominant protective immunity needed for leishmaniasis control. In conclusion, while centrin deficiency in L. braziliensis causes attenuation of virulence, and disrupts the ability to cause disease, it fails to stimulate a protective immune response. |
