Induction of autophagy correlates with increased parasite load of Leishmania amazonensis in BALB/c but not C57BL/6 macrophages |
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| Institution: | 1. Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21045-900, Brazil;2. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21944-970, Brazil;3. Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21944-970, Brazil;1. Centre de Recherche en Infectiologie, Université Laval, Québec, Canada;2. Glasgow Polyomics Facility, University of Glasgow, Glasgow, UK;3. Centro de Investigaciones Biológicas (CSIC), Madrid, Spain;4. Schools of Biology & Chemistry, Biomedical Sciences Research Complex (BSRC), The North Haugh, The University, St. Andrews, UK;1. Department of Medicine, Center for Emerging Pathogens, Rutgers, New Jersey Medical School, Newark, NJ, USA;2. Rutgers-Graduate School of Biomedical Sciences, Newark, NJ, USA;1. Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India;2. National Institute of Pharmaceutical Education and Research, Hajipur 844102, India;1. Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy;2. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Amadeo 42, 20133 Milan, Italy;3. Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B 07100 Sassari, Italy;4. Histology and Molecular Diagnostic, University Hospital Careggi, Viale G.B. Morgagni 85, 50134 Florence, Italy;5. Center for Research, Transfer and High Education ‘Study at Molecular and Clinical Level of Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development on Novel Therapies’, Italy;1. Departamento de Parasitologia, Microbiologia e Imunologia, I.C.B., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais, 36036-900, Brazil;2. Departamento de Química, I.C.E., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais, 36036-900, Brazil;3. Programa de Pós-graduação Em Modelagem Computacional, Departamento de Ciência da Computação, I.C.E., Universidade Federal Juiz de Fora, Juiz de Fora, Minas Gerais, 36036-900, Brazil;4. Programa de Pós-Graduação Em Ciências Biológicas, Universidade Estadual de Maringá, Maringá, Paraná, 87020-900, Brazil;5. Laboratorio de Imunofarmacologia, Instituto de Biof?sica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, 21941-902, Rio de Janeiro, Brazil;6. Escola de Ciências da Saúde, Universidade Do Grande Rio, 25071-202 Duque de Caxias, RJ, Brazil |
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| Abstract: | We investigated the role of autophagy in infection of macrophages by Leishmania amazonensis. Induction of autophagy by IFN-γ or starvation increased intracellular parasite load and the percentages of infected macrophages from BALB/c but not from C57BL/6 mice. In contrast, starvation did not affect the replication of either Leishmania major or Trypanosoma cruzi in BALB/c macrophages. In BALB/c macrophages, starvation resulted in increased monodansylcadaverine staining and in the appearance of double-membrane and myelin-like vesicles characteristic of autophagosomes. Increased parasite load was associated with a reduction in NO levels and was attenuated by wortmannin, an inhibitor of autophagy. In infected macrophages from BALB/c, but not from C57BL/6 mice, starvation increased the number of lipid bodies and the amounts of PGE2 produced. Exogenous PGE2 increased parasite load in macrophages from BALB/c, but not C57BL/6 mice. The cyclooxygenase inhibitor indomethacin prevented the increase of parasite load in starved BALB/c macrophages, and actually induced parasite killing. These results suggest that autophagy regulates the outcome of L. amazonensis infection in macrophages in a host strain specific manner. |
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