Journal article
Early Suppression of Macrophage Gene Expression by Leishmania braziliensis
Frontiers in microbiology, Vol.9, pp.2464-2464
10/15/2018
DOI: 10.3389/fmicb.2018.02464
PMCID: PMC6196312
PMID: 30374342
Abstract
Leishmania braziliensis
is an intracellular parasite that resides mostly in macrophages. Both the parasite genome and the clinical disease manifestations show considerable polymorphism. Clinical syndromes caused by
L. braziliensis
include localized cutaneous (CL), mucosal (ML), and disseminated leishmaniasis (DL). Our prior studies showed that genetically distinct
L. braziliensis
clades associate with different clinical types. Herein, we hypothesized that: (1)
L. braziliensis
induces changes in macrophage gene expression that facilitates infection; (2) infection of macrophages with strains associated with CL (clade B), ML (clade C), or DL (clade A) will differentially affect host cell gene expression, reflecting their different pathogenic mechanisms; and (3) differences between the strains will be reflected by differences in macrophage gene expression after initial exposure to the parasite. Human monocyte derived macrophages were infected with
L. braziliensis
isolates from clades A, B, or C. Patterns of gene expression were compared using Affymetrix DNA microarrays. Many transcripts were significantly decreased by infection with all isolates. The most dramatically decreased transcripts encoded proteins involved in signaling pathways, apoptosis, or mitochondrial oxidative phosphorylation. Some transcripts encoding stress response proteins were up-regulated. Differences between
L. braziliensis
clades were observed in the magnitude of change, rather than the identity of transcripts. Isolates from subjects with metastatic disease (ML and DL) induced a greater magnitude of change than isolates from CL. We conclude that
L. braziliensis
enhances its intracellular survival by inhibiting macrophage pathways leading to microbicidal activity. Parasite strains destined for dissemination may exert a more profound suppression than less invasive
L. braziliensis
strains that remain near the cutaneous site of inoculation.
Details
- Title: Subtitle
- Early Suppression of Macrophage Gene Expression by Leishmania braziliensis
- Creators
- Rosana Sousa - ,Viviane M Andrade - ,Thomas Bair - ,Nicholas A Ettinger - ,Luana Guimarães - ,Laura Andrade - ,Luiz H Guimarães - ,Paulo R. L Machado - ,Edgar M Carvalho - ,Mary E Wilson - ,Albert Schriefer - ,
- Resource Type
- Journal article
- Publication Details
- Frontiers in microbiology, Vol.9, pp.2464-2464
- DOI
- 10.3389/fmicb.2018.02464
- PMID
- 30374342
- PMCID
- PMC6196312
- NLM abbreviation
- Front Microbiol
- ISSN
- 1664-302X
- eISSN
- 1664-302X
- Publisher
- Frontiers Media S.A
- Grant note
- R03 A167663-01; P50 AI-30639 / National Institutes of Health I01BX001983; I01BX000536 / U.S. Department of Veterans Affairs
- Language
- English
- Date published
- 10/15/2018
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984001130702771
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