PMID- 19433541
OWN - NLM
STAT- MEDLINE
DCOM- 20090714
LR  - 20211020
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 77
IP  - 7
DP  - 2009 Jul
TI  - Overexpression of the natural inhibitor of cysteine peptidases in Leishmania 
      mexicana leads to reduced virulence and a Th1 response.
PG  - 2971-8
LID - 10.1128/IAI.00558-08 [doi]
AB  - 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 characterized, and ICP mutants have been created. Infection 
      of BALB/c mice with ICP null mutants or ICP reexpressing mutants resulted in 
      nonhealing, progressively growing lesions albeit slightly attenuated compared 
      with the growth of lesions produced by wild-type parasites. In contrast, BALB/c 
      mice infected with mutants overexpressing ICP were able to significantly control 
      lesion growth or heal. While BALB/c mice infected with wild-type parasites, ICP 
      null mutants, or ICP reexpressing mutants produced significant antibody 
      responses, including immunoglobulin E (IgE), no Th1 response, as indicated by 
      antigen-induced splenocyte gamma interferon (IFN-gamma) production, could be 
      demonstrated. In contrast, BALB/c mice infected with mutants overexpressing ICP 
      produced significantly less antibody, particularly IgE, as well as significantly 
      reduced splenocyte interleukin-4 and enhanced IFN-gamma production. BALB/c mice 
      were able to resolve infection following infection with one ICP overexpressing 
      clone, which was subsequently used for vaccination studies with BALB/c mice. 
      However, no protection was afforded these mice when they were challenged with 
      wild-type parasites. Nevertheless, two other mouse strains susceptible to L. 
      mexicana, C3H and C57BL/6, vaccinated with overexpressing 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.
FAU - Bryson, Karen
AU  - Bryson K
AD  - Strathclyde Institute of Pharmacy and Biomedical Sciences, University of 
      Strathclyde, Glasgow, United Kingdom.
FAU - Besteiro, Sebastien
AU  - Besteiro S
FAU - McGachy, H Adrienne
AU  - McGachy HA
FAU - Coombs, Graham H
AU  - Coombs GH
FAU - Mottram, Jeremy C
AU  - Mottram JC
FAU - Alexander, James
AU  - Alexander J
LA  - eng
GR  - G0700127/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090511
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antibodies, Protozoan)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Virulence Factors)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
SB  - IM
MH  - Animals
MH  - Antibodies, Protozoan/blood
MH  - Cysteine Endopeptidases/*metabolism
MH  - Cysteine Proteinase Inhibitors/*biosynthesis/genetics
MH  - Female
MH  - Gene Deletion
MH  - Genetic Complementation Test
MH  - Immunoglobulin E/blood
MH  - Interferon-gamma/metabolism
MH  - Leishmania mexicana/*immunology/*pathogenicity
MH  - Leishmaniasis, Cutaneous/immunology/*pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Severity of Illness Index
MH  - Spleen/immunology
MH  - Th1 Cells/*immunology
MH  - Virulence
MH  - Virulence Factors/*antagonists & inhibitors
PMC - PMC2708542
EDAT- 2009/05/13 09:00
MHDA- 2009/07/15 09:00
PMCR- 2010/01/01
CRDT- 2009/05/13 09:00
PHST- 2009/05/13 09:00 [entrez]
PHST- 2009/05/13 09:00 [pubmed]
PHST- 2009/07/15 09:00 [medline]
PHST- 2010/01/01 00:00 [pmc-release]
AID - IAI.00558-08 [pii]
AID - 0558-08 [pii]
AID - 10.1128/IAI.00558-08 [doi]
PST - ppublish
SO  - Infect Immun. 2009 Jul;77(7):2971-8. doi: 10.1128/IAI.00558-08. Epub 2009 May 11.