CCR2+ migratory macrophages with M1 status are the early-responders in the cornea of HSV-1 infected mice.

Complex interactions between HSV-1 and infiltrating immune cells play important roles in establishing localized, acute virus replication as well as chronic latent infection. The extent and duration of initial virus replication are the key determinants of subsequent pathologic inflammatory responses...

Full description

Bibliographic Details
Main Authors: Dhong Hyun Lee, Ujjaldeep Jaggi, Homayon Ghiasi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0215727
id doaj-70f0cd2e792c417fb8fd67e42d5b0185
record_format Article
spelling doaj-70f0cd2e792c417fb8fd67e42d5b01852021-03-03T20:43:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01144e021572710.1371/journal.pone.0215727CCR2+ migratory macrophages with M1 status are the early-responders in the cornea of HSV-1 infected mice.Dhong Hyun LeeUjjaldeep JaggiHomayon GhiasiComplex interactions between HSV-1 and infiltrating immune cells play important roles in establishing localized, acute virus replication as well as chronic latent infection. The extent and duration of initial virus replication are the key determinants of subsequent pathologic inflammatory responses and therefore, the accumulation of immune cell populations at this time point is a key target for prevention. Therefore, we evaluated the role of various immune cell infiltrates between 1 h and 28 days post-infection (PI) using mice infected with virulent HSV-1 strain McKrae without corneal scarification. The effect of corneal scarification on immune cell infiltrates was also determined. We first determined the activation status and origin of macrophage infiltrates as early as 1 h PI. We found a sharp increase in the total macrophage population after 12 h PI, that was primarily due to infiltration of CCR2+ migratory macrophages, mostly in M1 status (MHC II+). The number of CCR2- resident macrophages, mostly unpolarized (M0), increased gradually over time and peaked at 48 h PI. Interestingly, some of the resident macrophages gained an M2-like phenotype (CD206Low), which peaked at 12 h PI, concurrent with M1 macrophage infiltration. From 1-7 days PI, infiltration of various immune cells correlated strongly with HSV-1 replication, with neutrophils showing the biggest increase, and NKT cells the biggest decrease, after infection. The presence of geographical ulcer did not correlate with increased infiltration, while mice with corneal scarring had significantly more immune cell infiltration than those without corneal scarring. Overall, we showed time-dependent infiltration of various immune cells in the eye of HSV-1 infected mice. Initial infiltration of macrophages followed by infiltration of T cells at later times PI demonstrates the importance of targeting macrophages rather than other immune cells type, for therapeutic treatment of HSV-1.https://doi.org/10.1371/journal.pone.0215727
collection DOAJ
language English
format Article
sources DOAJ
author Dhong Hyun Lee
Ujjaldeep Jaggi
Homayon Ghiasi
spellingShingle Dhong Hyun Lee
Ujjaldeep Jaggi
Homayon Ghiasi
CCR2+ migratory macrophages with M1 status are the early-responders in the cornea of HSV-1 infected mice.
PLoS ONE
author_facet Dhong Hyun Lee
Ujjaldeep Jaggi
Homayon Ghiasi
author_sort Dhong Hyun Lee
title CCR2+ migratory macrophages with M1 status are the early-responders in the cornea of HSV-1 infected mice.
title_short CCR2+ migratory macrophages with M1 status are the early-responders in the cornea of HSV-1 infected mice.
title_full CCR2+ migratory macrophages with M1 status are the early-responders in the cornea of HSV-1 infected mice.
title_fullStr CCR2+ migratory macrophages with M1 status are the early-responders in the cornea of HSV-1 infected mice.
title_full_unstemmed CCR2+ migratory macrophages with M1 status are the early-responders in the cornea of HSV-1 infected mice.
title_sort ccr2+ migratory macrophages with m1 status are the early-responders in the cornea of hsv-1 infected mice.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2019-01-01
description Complex interactions between HSV-1 and infiltrating immune cells play important roles in establishing localized, acute virus replication as well as chronic latent infection. The extent and duration of initial virus replication are the key determinants of subsequent pathologic inflammatory responses and therefore, the accumulation of immune cell populations at this time point is a key target for prevention. Therefore, we evaluated the role of various immune cell infiltrates between 1 h and 28 days post-infection (PI) using mice infected with virulent HSV-1 strain McKrae without corneal scarification. The effect of corneal scarification on immune cell infiltrates was also determined. We first determined the activation status and origin of macrophage infiltrates as early as 1 h PI. We found a sharp increase in the total macrophage population after 12 h PI, that was primarily due to infiltration of CCR2+ migratory macrophages, mostly in M1 status (MHC II+). The number of CCR2- resident macrophages, mostly unpolarized (M0), increased gradually over time and peaked at 48 h PI. Interestingly, some of the resident macrophages gained an M2-like phenotype (CD206Low), which peaked at 12 h PI, concurrent with M1 macrophage infiltration. From 1-7 days PI, infiltration of various immune cells correlated strongly with HSV-1 replication, with neutrophils showing the biggest increase, and NKT cells the biggest decrease, after infection. The presence of geographical ulcer did not correlate with increased infiltration, while mice with corneal scarring had significantly more immune cell infiltration than those without corneal scarring. Overall, we showed time-dependent infiltration of various immune cells in the eye of HSV-1 infected mice. Initial infiltration of macrophages followed by infiltration of T cells at later times PI demonstrates the importance of targeting macrophages rather than other immune cells type, for therapeutic treatment of HSV-1.
url https://doi.org/10.1371/journal.pone.0215727
work_keys_str_mv AT dhonghyunlee ccr2migratorymacrophageswithm1statusaretheearlyrespondersinthecorneaofhsv1infectedmice
AT ujjaldeepjaggi ccr2migratorymacrophageswithm1statusaretheearlyrespondersinthecorneaofhsv1infectedmice
AT homayonghiasi ccr2migratorymacrophageswithm1statusaretheearlyrespondersinthecorneaofhsv1infectedmice
_version_ 1714820903718617088