Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major.

Inflammatory monocytes can be manipulated by environmental cues to perform multiple functions. To define the role of monocytes during primary or secondary infection with an intra-phagosomal pathogen we employed Leishmania major-red fluorescent protein (RFP) parasites and multi-color flow cytometry t...

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Main Authors: Audrey Romano, Matheus B H Carneiro, Nicole A Doria, Eric H Roma, Flavia L Ribeiro-Gomes, Ehud Inbar, Sang Hun Lee, Jonatan Mendez, Andrea Paun, David L Sacks, Nathan C Peters
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-06-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1006479
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author Audrey Romano
Matheus B H Carneiro
Nicole A Doria
Eric H Roma
Flavia L Ribeiro-Gomes
Ehud Inbar
Sang Hun Lee
Jonatan Mendez
Andrea Paun
David L Sacks
Nathan C Peters
author_facet Audrey Romano
Matheus B H Carneiro
Nicole A Doria
Eric H Roma
Flavia L Ribeiro-Gomes
Ehud Inbar
Sang Hun Lee
Jonatan Mendez
Andrea Paun
David L Sacks
Nathan C Peters
author_sort Audrey Romano
collection DOAJ
description Inflammatory monocytes can be manipulated by environmental cues to perform multiple functions. To define the role of monocytes during primary or secondary infection with an intra-phagosomal pathogen we employed Leishmania major-red fluorescent protein (RFP) parasites and multi-color flow cytometry to define and enumerate infected and uninfected inflammatory cells in the skin. During primary infection, infected monocytes had altered maturation and were the initial mononuclear host cell for parasite replication. In contrast, at a distal site of secondary infection in mice with a healed but persistent primary infection, this same population rapidly produced inducible nitric oxide synthase (iNOS) in an IFN-γ dependent manner and was critical for parasite killing. Maturation to a dendritic cell-like phenotype was not required for monocyte iNOS-production, and enhanced monocyte recruitment correlated with IFN-γ dependent cxcl10 expression. In contrast, neutrophils appeared to be a safe haven for parasites in both primary and secondary sites. Thus, inflammatory monocytes play divergent roles during primary versus secondary infection with an intra-phagosomal pathogen.
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spelling doaj.art-719e457dc0f44cb48b46e5d060e608112022-12-21T18:24:55ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-06-01136e100647910.1371/journal.ppat.1006479Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major.Audrey RomanoMatheus B H CarneiroNicole A DoriaEric H RomaFlavia L Ribeiro-GomesEhud InbarSang Hun LeeJonatan MendezAndrea PaunDavid L SacksNathan C PetersInflammatory monocytes can be manipulated by environmental cues to perform multiple functions. To define the role of monocytes during primary or secondary infection with an intra-phagosomal pathogen we employed Leishmania major-red fluorescent protein (RFP) parasites and multi-color flow cytometry to define and enumerate infected and uninfected inflammatory cells in the skin. During primary infection, infected monocytes had altered maturation and were the initial mononuclear host cell for parasite replication. In contrast, at a distal site of secondary infection in mice with a healed but persistent primary infection, this same population rapidly produced inducible nitric oxide synthase (iNOS) in an IFN-γ dependent manner and was critical for parasite killing. Maturation to a dendritic cell-like phenotype was not required for monocyte iNOS-production, and enhanced monocyte recruitment correlated with IFN-γ dependent cxcl10 expression. In contrast, neutrophils appeared to be a safe haven for parasites in both primary and secondary sites. Thus, inflammatory monocytes play divergent roles during primary versus secondary infection with an intra-phagosomal pathogen.https://doi.org/10.1371/journal.ppat.1006479
spellingShingle Audrey Romano
Matheus B H Carneiro
Nicole A Doria
Eric H Roma
Flavia L Ribeiro-Gomes
Ehud Inbar
Sang Hun Lee
Jonatan Mendez
Andrea Paun
David L Sacks
Nathan C Peters
Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major.
PLoS Pathogens
title Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major.
title_full Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major.
title_fullStr Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major.
title_full_unstemmed Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major.
title_short Divergent roles for Ly6C+CCR2+CX3CR1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen Leishmania major.
title_sort divergent roles for ly6c ccr2 cx3cr1 inflammatory monocytes during primary or secondary infection of the skin with the intra phagosomal pathogen leishmania major
url https://doi.org/10.1371/journal.ppat.1006479
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