Journal article
Altered dendritic cell phenotype in response to Leishmania amazonensis amastigote infection is mediated by MAP kinase, ERK
The American journal of pathology, Vol.174(5), pp.1818-1826
05/2009
DOI: 10.2353/ajpath.2009.080905
PMCID: PMC2671270
PMID: 19349356
Abstract
Initiation of productive immune responses against Leishmania depends on the successful transition of dendritic cells (DC) from an immature to a mature phenotype. This process is characterized by high CD40 surface expression as well as interleukin-12 production, which are frequently seen in response to L. major infection. In vivo footpad infection of C3HeB/FeJ mice for 7 days with L. amazonensis promoted an immature CD11c(+) DC phenotype characterized by both significantly low CD40 surface expression and significantly decreased interleukin-12p40 production compared with L. major infection of these same mice. In vitro infection of bone marrow-derived dendritic cells with L. amazonensis amastigotes resulted in rapid and significant phosphorylation of the mitogen activated protein kinase, extracellular signal-regulated kinase 1/2, observed within minutes of exposure to the parasite. Infection with L. amazonensis promastigotes led to increased 1/2 phosphorylation after 4 hours of infection compared with L. major infection, which correlated with promastigote transformation into amastigotes. Treatment of bone marrow-derived dendritic cells with a mitogen activated protein kinase kinase-specific inhibitor, PD98059, led to regained surface CD40 expression and interleukin-12p40 production following L. amazonensis amastigote infection compared with non-treated, infected DC. Treatment of L. amazonensis-infected mice with the highly-specific mitogen activated protein kinase kinase inhibitor, CI-1040, enhanced surface CD40 expression on CD11c(+) DC obtained from the draining lymph node. L. amazonensis amastigotes, through activation of extracellular signal-regulated kinase 1/2, inhibit the ability of DC to undergo proper maturation both in vitro and in vivo.
Details
- Title: Subtitle
- Altered dendritic cell phenotype in response to Leishmania amazonensis amastigote infection is mediated by MAP kinase, ERK
- Creators
- Paola Mercedes Boggiatto - Department of Veterinary Pathology, Iowa State University, Ames, Iowa 50011, USAFei JieMousumi Ghosh - Iowa State UniversityKatherine Nicole Gibson-CorleyAmanda Ellen Ramer-TaitDouglas Elliot JonesChristine Anne Petersen
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.174(5), pp.1818-1826
- DOI
- 10.2353/ajpath.2009.080905
- PMID
- 19349356
- PMCID
- PMC2671270
- NLM abbreviation
- Am J Pathol
- ISSN
- 1525-2191
- eISSN
- 1525-2191
- Publisher
- United States
- Grant note
- R21 AI074711 / NIAID NIH HHS AI48357 / NIAID NIH HHS K08 AI050803 / NIAID NIH HHS AI50803 / NIAID NIH HHS R01 AI048357 / NIAID NIH HHS
- Language
- English
- Date published
- 05/2009
- Academic Unit
- Epidemiology; Pathology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9983995029502771
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