Journal article
Leishmania-Derived Trimannose Modulates the Inflammatory Response To Significantly Reduce Leishmania major-Induced Lesions
Infection and immunity, Vol.86(1), e00672-17
2018
DOI: 10.1128/IAI.00672-17
PMCID: PMC5736800
PMID: 29061708
Abstract
Leishmania
lipophosphoglycan (LPG) is a key virulence factor, initiating inflammation resulting in cutaneous lesions. LPG is capped by various oligosaccharides. How these glycans are recognized and how they alter the course of
Leishmania
infection are poorly understood. Previous studies synthesized α-1,2-trimannose cap sugars on latex beads and demonstrated that C57BL/6 mice coinoculated with
Leishmania major
and trimannose-coated beads produced significantly higher levels of interleukin-12p40 (IL-12p40) and other proinflammatory, type 1 cytokines than mice inoculated with
L. major
alone within the first 48 h of infection. However, as
L. major
infection typically progress over weeks to months, the role of trimannose in altering disease progression over the course of infection was unknown. Wild-type mice were inoculated with either trimannose-coated or carrier (uncoated) beads, infected with
L. major
alone, coinoculated with carrier beads and
L. major
, or coinoculated with trimannose-coated beads and
L. major
. Trimannose treatment of
L. major
-infected mice decreased the parasite load and significantly decreased the lesion size at 14 days postinfection (p.i.) compared to results for nontreated, infected mice. Infected, trimannose-treated mice had decreased IL-12p40 and IL-10 secretion and increased interferon gamma secretion at 14 days p.i. Mannose receptor knockout (MR
−/−
) mice lack the ability to detect trimannose. When MR
−/−
mice were infected with
L. major
and treated with trimannose beads, they did not have decreased lesion size.
Leishmania
-derived trimannose represents a novel immunomodulator that provides early type 1-skewed cytokine production to control the parasite load and alter the course of cutaneous leishmaniasis.
Details
- Title: Subtitle
- Leishmania-Derived Trimannose Modulates the Inflammatory Response To Significantly Reduce Leishmania major-Induced Lesions
- Creators
- Tara L Grinnage-Pulley - Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa, USADaniel E. K Kabotso - Department of Chemistry, College of Arts and Sciences, Indiana University, Bloomington, Indiana, USAChelsea L Rintelmann - Department of Chemistry, College of Arts and Sciences, Indiana University, Bloomington, Indiana, USARajarshi Roychoudhury - Department of Chemistry, College of Arts and Sciences, Indiana University, Bloomington, Indiana, USARobert G Schaut - Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa, USAAngela J Toepp - Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa, USAKatherine N Gibson-Corley - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAMolly Parrish - Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa, USANicola L. B Pohl - Department of Chemistry, College of Arts and Sciences, Indiana University, Bloomington, Indiana, USAChristine A Petersen - Immunology Program, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.86(1), e00672-17
- DOI
- 10.1128/IAI.00672-17
- PMID
- 29061708
- PMCID
- PMC5736800
- NLM abbreviation
- Infect Immun
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Publisher
- American Society for Microbiology; 1752 N St., N.W., Washington, DC
- Grant note
- T32 GM109825 / ; Nanovaccine Initiative preliminary research grant / ; 5T32AI007511 / ;
- Alternative title
- Leishmania-Derived Trimannose Reduces L. major Lesions
- Language
- English
- Date published
- 2018
- Academic Unit
- Epidemiology; Pathology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9983995134602771
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