Mycobacterium leprae induces insulin-like growth factor and promotes survival of Schwann cells upon serum withdrawal.
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.
Rodrigues
Luciana Silva
LS
Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
da Silva Maeda
Elisa
E
Moreira
Maria Elisabete Costa
ME
Tempone
Antonio Jorge
AJ
Lobato
Lívia Silva
LS
Ribeiro-Resende
Victor Túlio
VT
Alves
Lucineia
L
Rossle
Shaila
S
Lopes
Ulisses Gazos
UG
Pessolani
Maria Cristina Vidal
MC
D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007120:Immunochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial; D009166:Mycobacterium leprae / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D007334:Insulin-Like Growth Factor I