Acanthamoeba activates macrophages predominantly through toll-like receptor 4 and MyD88-dependent mechanisms to induce Interleukin IL-12 and IL-6

Antonella Cano, Antonella Mattana, Stuart Woods, Fiona L. Henriquez, James Alexander, Craig W. Roberts

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Acanthamoeba castellanii is a free-living ubiquitous amoeba, with a worldwide distribution, that can occasionally infect humans, causing particularly severe infections in immune compromised individuals. Dissecting the immunology of Acanthamoeba infections has been considered problematic due to the very low incidence of disease despite the high exposure rates. Whilst macrophages are acknowledged as playing a significant role in Acanthamoeba infections little is known about how this facultative parasite influences macrophage activity. Therefore, in this study we investigate the effects of Acanthamoeba on the activation of resting macrophages. Consequently, murine bone marrow derived macrophages were co-cultured with trophozoites of either the laboratory Neff strain, or a clinical isolate of A. castellanii. In vitro real-time imaging demonstrated that trophozoites of both strains often established evanescent contact with macrophages. Both Acanthamoeba strains induced a pro-inflammatory macrophage phenotype characterized by significant production of IL-12 and IL-6. However, macrophages co-cultured with the clinical isolate of Acanthamoeba produced significantly less IL-12 and IL-6 in comparison to the Neff strain. The utilization of macrophages derived from MyD88, TRIF, TLR2, TLR4, TLR2/4 deficient mice indicated that Acanthamoeba-induced pro-inflammatory cytokine production was through MyD88-dependent, TRIF independent, TLR4-induced events. This study shows for the first time the involvement of TLRs, expressed on macrophages in the recognition and response to Acanthamoeba trophozoites.
LanguageEnglish
Article numbere01054-16
JournalInfection and Immunity
Volume85
Issue number6
Early online date27 Mar 2017
DOIs
Publication statusPublished - 30 Jun 2017

Fingerprint

Acanthamoeba
Toll-Like Receptor 4
Interleukin-12
Interleukin-6
Macrophages
Trophozoites
Acanthamoeba castellanii
Infection
Amoeba
Macrophage Activation
Allergy and Immunology
Parasites
Cytokines
Phenotype
Incidence

Keywords

  • Acanthamoeba castellanii
  • amoeba
  • macrophages
  • trophozoites
  • bone marrow
  • pro-inflammatory cytokine
  • toll like receptors

Cite this

@article{6b4af10c355f4e0daeb067fe83707976,
title = "Acanthamoeba activates macrophages predominantly through toll-like receptor 4 and MyD88-dependent mechanisms to induce Interleukin IL-12 and IL-6",
abstract = "Acanthamoeba castellanii is a free-living ubiquitous amoeba, with a worldwide distribution, that can occasionally infect humans, causing particularly severe infections in immune compromised individuals. Dissecting the immunology of Acanthamoeba infections has been considered problematic due to the very low incidence of disease despite the high exposure rates. Whilst macrophages are acknowledged as playing a significant role in Acanthamoeba infections little is known about how this facultative parasite influences macrophage activity. Therefore, in this study we investigate the effects of Acanthamoeba on the activation of resting macrophages. Consequently, murine bone marrow derived macrophages were co-cultured with trophozoites of either the laboratory Neff strain, or a clinical isolate of A. castellanii. In vitro real-time imaging demonstrated that trophozoites of both strains often established evanescent contact with macrophages. Both Acanthamoeba strains induced a pro-inflammatory macrophage phenotype characterized by significant production of IL-12 and IL-6. However, macrophages co-cultured with the clinical isolate of Acanthamoeba produced significantly less IL-12 and IL-6 in comparison to the Neff strain. The utilization of macrophages derived from MyD88, TRIF, TLR2, TLR4, TLR2/4 deficient mice indicated that Acanthamoeba-induced pro-inflammatory cytokine production was through MyD88-dependent, TRIF independent, TLR4-induced events. This study shows for the first time the involvement of TLRs, expressed on macrophages in the recognition and response to Acanthamoeba trophozoites.",
keywords = "Acanthamoeba castellanii, amoeba, macrophages, trophozoites, bone marrow, pro-inflammatory cytokine, toll like receptors",
author = "Antonella Cano and Antonella Mattana and Stuart Woods and Henriquez, {Fiona L.} and James Alexander and Roberts, {Craig W.}",
note = "Copyright {\circledC} 2017 American Society for Microbiology.",
year = "2017",
month = "6",
day = "30",
doi = "10.1128/IAI.01054-16",
language = "English",
volume = "85",
journal = "Infection and Immunity",
issn = "0019-9567",
number = "6",

}

Acanthamoeba activates macrophages predominantly through toll-like receptor 4 and MyD88-dependent mechanisms to induce Interleukin IL-12 and IL-6. / Cano, Antonella; Mattana, Antonella; Woods, Stuart; Henriquez, Fiona L.; Alexander, James; Roberts, Craig W.

In: Infection and Immunity , Vol. 85, No. 6, e01054-16, 30.06.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Acanthamoeba activates macrophages predominantly through toll-like receptor 4 and MyD88-dependent mechanisms to induce Interleukin IL-12 and IL-6

AU - Cano, Antonella

AU - Mattana, Antonella

AU - Woods, Stuart

AU - Henriquez, Fiona L.

AU - Alexander, James

AU - Roberts, Craig W.

N1 - Copyright © 2017 American Society for Microbiology.

PY - 2017/6/30

Y1 - 2017/6/30

N2 - Acanthamoeba castellanii is a free-living ubiquitous amoeba, with a worldwide distribution, that can occasionally infect humans, causing particularly severe infections in immune compromised individuals. Dissecting the immunology of Acanthamoeba infections has been considered problematic due to the very low incidence of disease despite the high exposure rates. Whilst macrophages are acknowledged as playing a significant role in Acanthamoeba infections little is known about how this facultative parasite influences macrophage activity. Therefore, in this study we investigate the effects of Acanthamoeba on the activation of resting macrophages. Consequently, murine bone marrow derived macrophages were co-cultured with trophozoites of either the laboratory Neff strain, or a clinical isolate of A. castellanii. In vitro real-time imaging demonstrated that trophozoites of both strains often established evanescent contact with macrophages. Both Acanthamoeba strains induced a pro-inflammatory macrophage phenotype characterized by significant production of IL-12 and IL-6. However, macrophages co-cultured with the clinical isolate of Acanthamoeba produced significantly less IL-12 and IL-6 in comparison to the Neff strain. The utilization of macrophages derived from MyD88, TRIF, TLR2, TLR4, TLR2/4 deficient mice indicated that Acanthamoeba-induced pro-inflammatory cytokine production was through MyD88-dependent, TRIF independent, TLR4-induced events. This study shows for the first time the involvement of TLRs, expressed on macrophages in the recognition and response to Acanthamoeba trophozoites.

AB - Acanthamoeba castellanii is a free-living ubiquitous amoeba, with a worldwide distribution, that can occasionally infect humans, causing particularly severe infections in immune compromised individuals. Dissecting the immunology of Acanthamoeba infections has been considered problematic due to the very low incidence of disease despite the high exposure rates. Whilst macrophages are acknowledged as playing a significant role in Acanthamoeba infections little is known about how this facultative parasite influences macrophage activity. Therefore, in this study we investigate the effects of Acanthamoeba on the activation of resting macrophages. Consequently, murine bone marrow derived macrophages were co-cultured with trophozoites of either the laboratory Neff strain, or a clinical isolate of A. castellanii. In vitro real-time imaging demonstrated that trophozoites of both strains often established evanescent contact with macrophages. Both Acanthamoeba strains induced a pro-inflammatory macrophage phenotype characterized by significant production of IL-12 and IL-6. However, macrophages co-cultured with the clinical isolate of Acanthamoeba produced significantly less IL-12 and IL-6 in comparison to the Neff strain. The utilization of macrophages derived from MyD88, TRIF, TLR2, TLR4, TLR2/4 deficient mice indicated that Acanthamoeba-induced pro-inflammatory cytokine production was through MyD88-dependent, TRIF independent, TLR4-induced events. This study shows for the first time the involvement of TLRs, expressed on macrophages in the recognition and response to Acanthamoeba trophozoites.

KW - Acanthamoeba castellanii

KW - amoeba

KW - macrophages

KW - trophozoites

KW - bone marrow

KW - pro-inflammatory cytokine

KW - toll like receptors

UR - http://www.scopus.com/inward/record.url?scp=85019898983&partnerID=8YFLogxK

U2 - 10.1128/IAI.01054-16

DO - 10.1128/IAI.01054-16

M3 - Article

VL - 85

JO - Infection and Immunity

T2 - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 6

M1 - e01054-16

ER -