| Apicomplexan parasite, Eimeria falciformis, co-opts host tryptophan catabolism for life cycle progression in mouse. | |
| | |
MedLine Citation:
|
PMID: 22535959 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The obligate intracellular apicomplexan parasites, e.g. Toxoplasma gondii and Plasmodium species, induce an IFNγ-driven induction of host indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme of tryptophan catabolism in the kynurenine pathway. Induction of IDO1 supposedly depletes cellular levels of tryptophan in host cells, which is proposed to inhibit the in vitro growth of auxotrophic pathogens. In vivo function of IDO during infections, however, is not clear, let alone controversial. We show that Eimeria falciformis, an apicomplexan parasite infecting the mouse caecum, induces IDO1 in the epithelial cells of the organ, and the enzyme expression coincides with the parasite development. The absence or inhibition of IDO1/2 and of two downstream enzymes in infected animals is detrimental to the Eimeria growth. The reduced parasite yield is not due to a lack of an immunosuppressive effect of IDO1 in the parasitized IDO1(-/-) or inhibitor-treated mice because they did not show an accentuated Th1 and IFNγ response. Noticeably, the parasite development is entirely rescued by xanthurenic acid, a by-product of tryptophan catabolism inducing exflagellation in male gametes of Plasmodium in the mosquito mid-gut. Our data demonstrate a conceptual subversion of the host defense (IFNγ, IDO) by an intracellular pathogen for progression of its natural life cycle. Besides, we show utility of E. falciformis, a monoxenous parasite of a well appreciated host, i.e. mouse, to identify in vivo factors underlying the parasite-host interactions. |
| | |
Authors:
|
Manuela Schmid; Maik J Lehmann; Richard Lucius; Nishith Gupta |
Related Documents
:
|
23427509 - Group a streptococcal tonsillopharyngitis burden in a tertiary turkish hospital. 23493659 - Narcolepsy-cataplexy: is streptococcal infection a trigger? 22521209 - The role of parasites and pathogens in influencing generalised anxiety and predation-re... 21437649 - Genetic analysis in mice identifies cysteamine as a novel partner for artemisinin in th... 21120729 - Neonatal herpes simplex virus infections: where are we now? 22981919 - Mdm2 regulates a novel form of incomplete neoplastic transformation of theileria parva ... 23673249 - Infections by babesia caballi and theileria equi in jordanian equids: epidemiology and ... 11349029 - Analysis of mechanisms associated with loss of infectivity of clonal populations of bor... 19647339 - Microbiology of wound infections among hospitalised patients following the 2005 pakista... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-04-25 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Jun |
Date Detail:
|
Created Date: 2012-06-11 Completed Date: 2012-09-21 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 20197-207 Citation Subset: IM |
Affiliation:
|
Department of Molecular Parasitology, Humboldt University, 10115 Berlin, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Coccidiosis / genetics, immunology, metabolism* Culicidae / parasitology Eimeria / genetics, immunology, metabolism* Enzyme Inhibitors / pharmacology Hypolipidemic Agents / pharmacology Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors, genetics, immunology*, metabolism Interferon-gamma / genetics, immunology, metabolism Mice Mice, Inbred BALB C Mice, Knockout Th1 Cells / immunology, metabolism* Tryptophan / genetics, immunology, metabolism* Xanthurenates / pharmacology |
| Chemical | |
Reg. No./Substance:
|
0/Enzyme Inhibitors; 0/Hypolipidemic Agents; 0/Indoleamine-Pyrrole 2,3,-Dioxygenase; 0/Xanthurenates; 58LAB1BG8J/xanthurenic acid; 73-22-3/Tryptophan; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: ?-Subunit of the Ost?-Ost? organic solute transporter is required not only for heterodimerization an...
Next Document: Use of structural phylogenetic networks for classification of the ferritin-like superfamily.