Bryson, K., Besteiro, S., McGachy, H. A., Coombs, G. H., Mottram, J. C. and Alexander, J. (2009) Overexpression of the natural inhibitor of cysteine peptidases, ICP, in Leishmania mexicana leads to reduced virulence and a Th1 response. Infection and Immunity, 77(7), pp. 2971-2978. (doi: 10.1128/IAI.00558-08) (PMID:19433541) (PMCID:PMC2708542)
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Abstract
Leishmania mexicana cysteine peptidases (CPs) have been identified as important parasite virulence factors. More recently a natural inhibitor of CPs (ICP) from L. mexicana has been characterised and ICP mutants have been created. Infection of BALB/c mice with ICP null mutants or ICP re-expressing mutants resulted in non-healing progressively growing lesions albeit slightly attenuated compared with the growth of wild-type parasites. In contrast BALB/c mice infected with mutants over-expressing ICP were able to significantly control lesion growth or heal. While BALB/c mice infected with wild-type parasites, ICP null mutants or ICP re-expressing mutants produced significant antibody responses including IgE, no Th1 response as indicated by antigen-induced splenocyte IFN-{gamma} production could be demonstrated. In contrast, BALB/c mice infected with mutants over-expressing ICP produced significantly less antibody, particularly IgE, as well as significantly reduced splenocyte IL-4, and enhanced IFN-{gamma} production. BALB/c mice were able to resolve infection following infection with one ICP over-expressing clone, which was subsequently used for vaccination studies in BALB/c mice. However, no protection was afforded these mice when they were challenged with wild-type parasites. Nevertheless, 2 other mouse strains susceptible to L. mexicana, C3H and C57BL/6, vaccinated with over-expressing ICP mutants were able to control challenge infection associated with an enhanced Th1 response. This study confirms that L. mexicana CPs are virulence factors and that ICPs have therapeutic potential
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Bryson, Dr Karen and Mottram, Professor Jeremy and Coombs, Professor Graham |
| Authors: | Bryson, K., Besteiro, S., McGachy, H. A., Coombs, G. H., Mottram, J. C., and Alexander, J. |
| Subjects: | Q Science > QR Microbiology > QR180 Immunology |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Infection and Immunity |
| Journal Abbr.: | IAI |
| Publisher: | American Society for Microbiology |
| ISSN: | 0019-9567 |
| ISSN (Online): | 1098-5522 |
| Published Online: | 11 May 2009 |
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