Mycobacterium leprae induces insulin-like growth factor and promotes survival of Schwann cells upon serum withdrawal |
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Authors: | Luciana Silva Rodrigues Elisa da Silva Maeda Maria Elisabete Costa Moreira Antonio Jorge Tempone Lívia Silva Lobato Victor Túlio Ribeiro-Resende Lucineia Alves Shaila Rossle Ulisses Gazos Lopes Maria Cristina Vidal Pessolani |
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Institution: | Laboratory of Cellular Microbiology, Instituto Oswaldo Cruz, Rio de Janeiro, RJ 21045-900, Brazil.; Laboratory of Experimental Medicine, Instituto Nacional do Câncer, Rio de Janeiro, RJ 20230-130, Brazil.; Laboratory of Molecular Parasitology, Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro, RJ 21941-902, Brazil. |
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Abstract: | Peripheral nerve lesions are considered the most relevant symptoms of leprosy, a chronic infectious disease caused by Mycobacterium leprae . The strategies employed by M. leprae to infect and multiply inside Schwann cells (SCs), however, remain poorly understood. In this study, it is shown that treatment of SCs with M. leprae significantly decreased cell death induced by serum deprivation. Not displayed by Mycobacterium smegmatis or Mycobacterium bovis BCG , the M. leprae survival effect was both dose dependent and specific . The conditioned medium (CM) of M. leprae -treated cultures was seen to mimic the protective effect of the bacteria, suggesting that soluble factors secreted by SCs in response to M. leprae were involved in cell survival. Indeed, by quantitative RT-PCR and dot blot/ELISA, it was demonstrated that M. leprae induced the expression and secretion of the SC survival factor insulin-like growth factor-I. Finally, the involvement of this hormone in M. leprae -induced SC survival was confirmed in experiments with neutralizing antibodies. Taken together, the results of this study delineate an important strategy for the successful colonization of M. leprae in the nerve based on the survival maintenance of the host cell through induction of IGF-I production. |
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