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Leishmania major induces secretion of inflammatory cytokines and chemokines by keratinocytes via a TLR2 pathway

Abstract number: 1732_116

Ronet C., Bakhiet S., Pavlin C., Akira S., Launois P.

Objectives: Some features of the cutaneous pathologies observed in patients with cutaneous leishmaniasis can be reproduced in the murine model of infection with L. major. After subcutaneous injection of parasites in C57BL/6, mice are resistant to infection; in contrast BALB/c mice are susceptible to infection. Resistance and susceptibility to the infection were related to the development of polarised Th1 and Th2 response. Keratinocytes are the first effector cells encountering parasites during infection with L. major but their role in the initiation of the immune response is mainly ignored. The aim of this study is to analyse the role of the interaction between L. major and keratinocytes in the subsequent immune response induced by infection with this parasite.

Methods: Cultured primary murine keratinocytes from neonatal C57BL/6 and BALB/c mice (1–3 days old) were stimulated in vitro by L. major LV39 strain (MHRO/Sv/59/P strain), and mRNA expression and secretion of inflammatory cytokines (IL-1, IL-6 and TNF-a) and chemokines (MIP-2) were analysed.

Results: Parasites adhere to keratinocytes through the flagellar tip, the flagellar base or with the posterior pole in both strains of mice, but they never infect keratinocytes. Whereas this interaction induces an up-regulation of IL-1 and MIP-2 mRNA expression and secretion in both BALB/c and C57BL/6 mice, IL-6 is produced in response to L. major only in BALB/c mice. Furthermore, we demonstrated that TLR-2 -/- mice are unable to produce MIP-2 in response to L. major stimulation.

Conclusion: The results strongly suggest that keratinocytes are able to produce cytokines in response to L. major stimulation through in part-TLR-2.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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