We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Distinct Transcriptional Signatures of Bone Marrow-Derived C57BL/6 and DBA/2 Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes.
- Authors
Giraud, Emilie; Lecoeur, Hervé; Soubigou, Guillaume; Coppée, Jean-Yves; Milon, Geneviève; Prina, Eric; Lang, Thierry
- Abstract
Background/Objectives: The inoculation of a low number (104) of L. amazonensis metacyclic promastigotes into the dermis of C57BL/6 and DBA/2 mouse ear pinna results in distinct outcome as assessed by the parasite load values and ear pinna macroscopic features monitored from days 4 to 22-phase 1 and from days 22 to 80/100-phase 2. While in C57BL/6 mice, the amastigote population size was increasing progressively, in DBA/2 mice, it was rapidly controlled. This latter rapid control did not prevent intracellular amastigotes to persist in the ear pinna and in the ear-draining lymph node/ear-DLN. The objectives of the present analysis was to compare the dendritic leukocytes-dependant immune processes that could account for the distinct outcome during the phase 1, namely, when phagocytic dendritic leucocytes of C57BL/6 and DBA/2 mice have been subverted as live amastigotes-hosting cells. Methodology/Principal Findings: Being aware of the very low frequency of the tissues' dendritic leucocytes/DLs, bone marrow-derived C57BL/6 and DBA/2 DLs were first generated and exposed or not to live DsRed2 expressing L. amazonensis amastigotes. Once sorted from the four bone marrow cultures, the DLs were compared by Affymetrix-based transcriptomic analyses and flow cytometry. C57BL/6 and DBA/2 DLs cells hosting live L. amazonensis amastigotes do display distinct transcriptional signatures and markers that could contribute to the distinct features observed in C57BL/6 versus DBA/2 ear pinna and in the ear pinna-DLNs during the first phase post L. amazonensis inoculation. Conclusions/Significance: The distinct features captured in vitro from homogenous populations of C57BL/6 and DBA/2 DLs hosting live amastigotes do offer solid resources for further comparing, in vivo, in biologically sound conditions, functions that range from leukocyte mobilization within the ear pinna, the distinct emigration from the ear pinna to the DLN of live amastigotes-hosting DLs, and their unique signalling functions to either naive or primed T lymphocytes. Author Summary: The rapid and long term establishment of parasites such as L. amazonensis, otherwise known to strictly rely on subversion of macrophage and dendritic leucocyte (DL) lineages, is expected to reflect stepwise processes taking place in both the skin dermis where the infective form of the parasite and the skin-draining lymph node (DLN) were inoculated. Relying on mice of two distinct inbred strains—C57BL/6 and DBA/2—that rapidly and durably display distinct phenotypes at the two sites of establishment of L. amazonensis, we were curious to address the following question: could live L. amazonensis-hosting DL display unique signatures that account for the distinct phenotypes? Based on flow cytometry, genechip and real-time quantitative PCR analyses, our results did evidence that, once subverted as cells hosting live L. amazonensis, DLs from C57BL/6 or DBA/2 do display distinct profiles that could account for the i) distinct parasite load profiles, ii) as well as the distinct macroscopic features of ear pinna observed once the L. amazonensis metacyclic promastigotes completed their four day developmental program along the amastigote morphotype.
- Subjects
LEUCOCYTES; AMASTIGOTES; EAR; T cells; LABORATORY mice; DEVELOPMENTAL programs; BONE marrow; LEISHMANIA mexicana
- Publication
PLoS Neglected Tropical Diseases, 2012, Vol 6, Issue 12, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0001980