PMID- 28490589
OWN - NLM
STAT- MEDLINE
DCOM- 20170726
LR  - 20181202
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 91
IP  - 15
DP  - 2017 Aug 1
TI  - Roles of M1 and M2 Macrophages in Herpes Simplex Virus 1 Infectivity.
LID - 10.1128/JVI.00578-17 [doi]
LID - e00578-17
AB  - Macrophages are the predominant infiltrate in the corneas of mice that have been 
      ocularly infected with herpes simplex virus 1 (HSV-1). However, very little is 
      known about the relative roles of M1 (classically activated or polarized) and M2 
      (alternatively activated or polarized) macrophages in ocular HSV-1 infection. To 
      better understand these relationships, we assessed the impact of directed M1 or 
      M2 activation of RAW264.7 macrophages and peritoneal macrophages (PM) on 
      subsequent HSV-1 infection. In both the RAW264.7 macrophage and PM in vitro 
      models, HSV-1 replication in M1 macrophages was markedly lower than in M2 
      macrophages and unstimulated controls. The M1 macrophages expressed significantly 
      higher levels of 28 of the 32 tested cytokines and chemokines than M2 
      macrophages, with HSV-1 infection significantly increasing the levels of 
      proinflammatory cytokines and chemokines in the M1 versus the M2 macrophages. To 
      examine the effects of shifting the immune response toward either M1 or M2 
      macrophages in vivo, wild-type mice were injected with gamma interferon (IFN-gamma) 
      DNA or colony-stimulating factor 1 (CSF-1) DNA prior to ocular infection with 
      HSV-1. Virus replication in the eye, latency in trigeminal ganglia (TG), and 
      markers of T cell exhaustion in the TG were determined. We found that injection 
      of mice with IFN-gamma DNA, which enhances the development of M1 macrophages, 
      increased virus replication in the eye; increased latency; and also increased 
      CD4, CD8, IFN-gamma, and PD-1 transcripts in the TG of latently infected mice. 
      Conversely, injection of mice with CSF-1 DNA, which enhances the development of 
      M2 macrophages, was associated with reduced virus replication in the eye and 
      reduced latency and reduced the levels of CD4, CD8, IFN-gamma,and PD-1 transcripts in 
      the TG. Collectively, these results suggest that M2 macrophages directly reduce 
      the levels of HSV-1 latency and, thus, T-cell exhaustion in the TG of ocularly 
      infected mice.IMPORTANCE Our findings demonstrate a novel approach to further 
      reducing HSV-1 replication in the eye and latency in the TG by modulating immune 
      components, specifically, by altering the phenotype of macrophages. We suggest 
      that inclusion of CSF-1 as part of any vaccination regimen against HSV infection 
      to coax responses of macrophages toward an M2, rather than an M1, response may 
      further improve vaccine efficacy against ocular HSV-1 replication and latency.
CI  - Copyright (c) 2017 American Society for Microbiology.
FAU - Lee, Dhong Hyun
AU  - Lee DH
AD  - Center for Neurobiology and Vaccine Development, Ophthalmology Research, 
      Department of Surgery, Cedars-Sinai Burns and Allen Research Institute, Los 
      Angeles, California, USA.
FAU - Ghiasi, Homayon
AU  - Ghiasi H
AD  - Center for Neurobiology and Vaccine Development, Ophthalmology Research, 
      Department of Surgery, Cedars-Sinai Burns and Allen Research Institute, Los 
      Angeles, California, USA ghiasih@cshs.org.
LA  - eng
GR  - R01 EY024649/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20170712
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Cytokines)
SB  - IM
CIN - J Virol. 2017 Oct 13;91(21):. PMID: 29030534
CIN - J Virol. 2017 Oct 13;91(21):. PMID: 29030535
MH  - Animals
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Herpesvirus 1, Human/*physiology
MH  - Keratitis, Herpetic/*immunology/*virology
MH  - Macrophages/*virology
MH  - Mice
MH  - Trigeminal Ganglion/virology
MH  - Virus Latency
MH  - *Virus Replication
PMC - PMC5512262
OTO - NOTNLM
OT  - CSF-1
OT  - HSV-1
OT  - IFN-gamma
OT  - exhaustion
OT  - infectivity
OT  - latency
OT  - macrophages
OT  - polarized
OT  - primary infection
OT  - reactivation
EDAT- 2017/05/12 06:00
MHDA- 2017/07/27 06:00
PMCR- 2018/01/12
CRDT- 2017/05/12 06:00
PHST- 2017/04/05 00:00 [received]
PHST- 2017/05/03 00:00 [accepted]
PHST- 2017/05/12 06:00 [pubmed]
PHST- 2017/07/27 06:00 [medline]
PHST- 2017/05/12 06:00 [entrez]
PHST- 2018/01/12 00:00 [pmc-release]
AID - JVI.00578-17 [pii]
AID - 00578-17 [pii]
AID - 10.1128/JVI.00578-17 [doi]
PST - epublish
SO  - J Virol. 2017 Jul 12;91(15):e00578-17. doi: 10.1128/JVI.00578-17. Print 2017 Aug 
      1.