Differential Activation of Human Keratinocytes by Leishmania Species Causing Localized or Disseminated Disease

Breanna M Scorza; Mark A Wacker; Kelly Messingham; Peter Kim; Aloysius Klingelhutz; Janet Fairley; Mary E Wilson

doi:10.1016/j.jid.2017.05.028

Back

Differential Activation of Human Keratinocytes by Leishmania Species Causing Localized or Disseminated Disease

Journal article

Open access

Peer reviewed

Differential Activation of Human Keratinocytes by Leishmania Species Causing Localized or Disseminated Disease

Breanna M Scorza, Mark A Wacker, Kelly Messingham, Peter Kim, Aloysius Klingelhutz, Janet Fairley and Mary E Wilson

Journal of investigative dermatology, Vol.137(10), pp.2149-2156

10/2017

DOI: 10.1016/j.jid.2017.05.028

PMCID: PMC5786447

PMID: 28647347

Files and links (1)

url

https://doi.org/10.1016/j.jid.2017.05.028View

Published (Version of record) Open Access

Abstract

All Leishmania species parasites are introduced into mammalian skin through a sand fly bite, but different species cause distinct clinical outcomes. Mouse studies suggest that early responses are critical determinants of subsequent adaptive immunity in leishmaniasis, yet few studies address the role of keratinocytes, the most abundant cell in the epidermis. We hypothesized that Leishmania infection causes keratinocytes to produce immunomodulatory factors that influence the outcome of infection. Incubation of primary or immortalized human keratinocytes with Leishmania infantum or Leishmania major, which cause visceral or cutaneous leishmaniasis, respectively, elicited dramatically different responses. Keratinocytes incubated with L. infantum significantly increased expression of proinflammatory genes for IL-6, IL-8, tumor necrosis factor, and IL-1B, whereas keratinocytes exposed to several L. major isolates did not. Furthermore, keratinocyte-monocyte co-incubation studies across a 4 µM semipermeable membrane suggested that L. infantum-exposed keratinocytes release soluble factors that enhance monocyte control of intracellular L. infantum replication (P < 0.01). L. major-exposed keratinocytes had no comparable effect. These data suggest that L. infantum and L. major differentially activate keratinocytes to release factors that limit infection in monocytes. We propose that keratinocytes initiate or withhold a proinflammatory response at the site of infection, generating a microenvironment uniquely tailored to each Leishmania species that may affect the course of disease.

TNF

NHSK1

Details

Title: Subtitle: Differential Activation of Human Keratinocytes by Leishmania Species Causing Localized or Disseminated Disease
Creators: Breanna M Scorza - University of Iowa, Interdisciplinary Graduate Program in Immunology, Iowa City, Iowa, USA
Mark A Wacker - University of Iowa, Department of Internal Medicine, Iowa City, Iowa, USA
Kelly Messingham - University of Iowa, Department of Dermatology, Iowa City, Iowa, USA
Peter Kim - University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
Aloysius Klingelhutz - University of Iowa, Department of Microbiology, Iowa City, Iowa, USA
Janet Fairley - University of Iowa, Department of Dermatology, Iowa City, Iowa, USA
Mary E Wilson - University of Iowa, Interdisciplinary Graduate Program in Immunology, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Journal of investigative dermatology, Vol.137(10), pp.2149-2156
DOI: 10.1016/j.jid.2017.05.028
PMID: 28647347
PMCID: PMC5786447
NLM abbreviation: J Invest Dermatol
ISSN: 0022-202X
eISSN: 1523-1747
Publisher: Elsevier Inc
Language: English
Date published: 10/2017
Academic Unit: Dermatology; Microbiology and Immunology; International Programs; Epidemiology; Radiation Oncology; Internal Medicine
Record Identifier: 9984001203902771

Metrics

22 Record Views

29 Times Cited - Web of Science