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Leishmania major large RAB GTPase is highly immunogenic in individuals immune to cutaneous and visceral leishmaniasis.

Abstract We previously identified a Leishmania (L.) major large RAB GTPase (LmlRAB), a new atypical RAB GTPase protein. It is highly conserved in Leishmania species while displaying low level of homology with mammalian homologues. Leishmania small RAB GTPases proteins have been involved in regulation of exocytic and endocytic pathways whereas the role of large RAB GTPases proteins has not been characterized yet. We report here the immunogenicity of both recombinant rLmlRAB and rLmlRABC, in individuals with immunity against L. major or L. infantum.
PMID
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Authors

Mayor MeshTerms
Keywords

Cross-protection

Human leishmaniasis

Leishmania

RAB GTPase

Vaccine

Journal Title parasites & vectors
Publication Year Start




PMID- 28416006
OWN - NLM
STAT- MEDLINE
DA  - 20170418
DCOM- 20170425
LR  - 20170425
IS  - 1756-3305 (Electronic)
IS  - 1756-3305 (Linking)
VI  - 10
IP  - 1
DP  - 2017 Apr 17
TI  - Leishmania major large RAB GTPase is highly immunogenic in individuals immune to 
      cutaneous and visceral leishmaniasis.
PG  - 185
LID - 10.1186/s13071-017-2127-3 [doi]
AB  - BACKGROUND: We previously identified a Leishmania (L.) major large RAB GTPase
      (LmlRAB), a new atypical RAB GTPase protein. It is highly conserved in Leishmania
      species while displaying low level of homology with mammalian homologues.
      Leishmania small RAB GTPases proteins have been involved in regulation of
      exocytic and endocytic pathways whereas the role of large RAB GTPases proteins
      has not been characterized yet. We report here the immunogenicity of both
      recombinant rLmlRAB and rLmlRABC, in individuals with immunity against L. major
      or L. infantum. METHODS: PBMC were isolated from individuals cured of L. major
      (CCLm) or from healthy individuals. The latter were subdivided into high or low
      IFN-gamma responders. Healthy high IFN-gamma responders, considered as
      asymptomatics, were living in an endemic area for L. major (HHRLm) or L. infantum
      (HHRLi). Healthy low IFN-gamma responders (HLR) were considered as naive
      controls. Cells from all volunteers were stimulated with rLmlRAB or rLmlRABC.
      Cytokines were analysed by CBA and ELISA and phenotypes of IFN-gamma-producing
      cells were analysed by flow cytometry. RESULTS: Both rLmlRAB and rLmlRABC induced
      high significant levels of IFN-gamma in CCLm, HHRLm and HHRLi groups. Phenotype
      analysis of rLmlRAB and rLmlRABC-stimulated T cells in CCLm individuals showed a 
      significant increase in the percentage of specific IFN-gamma-producing CD4+ and
      CD8+ T cells. rLmlRAB induced significant granzyme B levels in CCLm and HHRLm.
      Low but significant granzyme B levels were detected in naive group. IL-10 was
      detected in immune and naive individuals. CONCLUSION: We showed that rLmlRAB
      protein and its divergent carboxy-terminal part induced a predominant Th1
      response in individuals immune to L. major or L. infantum. Our results suggest
      that rLmlRAB and rLmlRABC proteins are potential cross-species vaccine candidates
      against cutaneous and visceral leishmaniasis.
FAU - Chamakh-Ayari, Rym
AU  - Chamakh-Ayari R
AD  - Laboratory of Medical Parasitology, Biotechnology and Biomolecules, LR11-IPT-06, 
      Institut Pasteur de Tunis, Tunis, Tunisia.
AD  - University of Carthage, Tunis, Tunisia.
FAU - Chenik, Mehdi
AU  - Chenik M
AD  - Laboratory of Medical Parasitology, Biotechnology and Biomolecules, LR11-IPT-06, 
      Institut Pasteur de Tunis, Tunis, Tunisia.
FAU - Chakroun, Ahmed Sahbi
AU  - Chakroun AS
AD  - Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases 
      Laboratory, Institut Pasteur de Tunis, Tunis, Tunisia.
FAU - Bahi-Jaber, Narges
AU  - Bahi-Jaber N
AD  - Institut Polytechnique LaSalle Beauvais, Beauvais, France.
FAU - Aoun, Karim
AU  - Aoun K
AD  - Laboratory of Medical Parasitology, Biotechnology and Biomolecules, LR11-IPT-06, 
      Institut Pasteur de Tunis, Tunis, Tunisia.
FAU - Meddeb-Garnaoui, Amel
AU  - Meddeb-Garnaoui A
AD  - Laboratory of Medical Parasitology, Biotechnology and Biomolecules, LR11-IPT-06, 
      Institut Pasteur de Tunis, Tunis, Tunisia. [email protected]
LA  - eng
PT  - Journal Article
DEP - 20170417
PL  - England
TA  - Parasit Vectors
JT  - Parasites & vectors
JID - 101462774
RN  - 0 (Cytokines)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cytokines/secretion
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Humans
MH  - Leishmania major/*enzymology/*immunology
MH  - Leishmaniasis/*immunology
MH  - Leukocytes, Mononuclear/*immunology
MH  - Middle Aged
MH  - Young Adult
MH  - rab GTP-Binding Proteins/*immunology
PMC - PMC5393016
OTO - NOTNLM
OT  - Cross-protection
OT  - Human leishmaniasis
OT  - Leishmania
OT  - RAB GTPase
OT  - Vaccine
EDAT- 2017/04/19 06:00
MHDA- 2017/04/26 06:00
CRDT- 2017/04/19 06:00
PHST- 2016/07/19 [received]
PHST- 2017/04/04 [accepted]
AID - 10.1186/s13071-017-2127-3 [doi]
AID - 10.1186/s13071-017-2127-3 [pii]
PST - epublish
SO  - Parasit Vectors. 2017 Apr 17;10(1):185. doi: 10.1186/s13071-017-2127-3.

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