The role of classical and alternative macrophages in the immunopathogenesis of herpes simplex virus-induced inflammation in a mouse model

Anower, A. K. M. M.; Shim, Joongpyo; Choi, Bunsoon; Kwon, Hyuk Jae; Sohn, Seonghyang

doi:10.1016/j.jdermsci.2013.11.001

Cited by 25 publications

(17 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Shifting of the macrophage subtypes may affect the the process of EAU. Decrease of M1 subtype but increase of M2 subtype may confer beneficial effects to EAU3637. Thus, to investigate whether ACE2 would regulate the polarization of the macrophage subtype locally and systemically, typical surface markers of M1 (iNOS) and M2 (Arginase-1) macrophages were detected by real-time PCR.…”

Section: Resultsmentioning

confidence: 99%

“…A shift of macrophages from the M1 to M2 phenotype reduces the experimental inflammatory colitis60. Downregulating the M1/M2 ratio of macrophage has been shown to attenuate the Behçet’s disease (BD)-like symptoms in a herpes simplex virus (HSV)-induced inflammatory mouse model36. Further, IL-33 increases the frequency of M2 macrophages in the lymphoid organs confers a protective effect in EAU37.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways

Qiu

Tao

Zheng

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Renin angiotensin system (RAS) is a key hormonal system which regulates the cardiovascular function and is implicated in several autoimmune diseases. With the discovery of the angiotensin-converting enzyme 2 (ACE2), a protective axis of RAS namely ACE2/Ang-(1–7)/Mas that counteracts the deleterious ACE/AngII/AT1R axis has been established. This axis is emerging as a novel target to attenuate ocular inflammation. However, the underlying molecular mechanisms remain unclear. We investigated the hypothesis that enhancing the activity of the protective axis of RAS by subretinal delivery of an AAV8 (Y733F)-ACE2 vector would protect against the ocular inflammation in experimental autoimmune uveitis (EAU) mice through regulating the local immune responses. Our studies demonstrated that increased ACE2 expression exerts protective effects on inflammation in EAU mouse by modulating ocular immune responses, including the differentiation of Th1/Th17 cells and the polarization of M1/M2 macrophages; whereas the systemic immune responses appeared not affected. These effects were mediated by activating the Ang-(1–7)/Mas and inhibiting the MAPK, NF-κB and STAT3 signaling pathways. This proof-of-concept study suggests that activation of ocular ACE2/Ang-(1–7)/Mas axis with AAV gene transfer modulates local immune responses and may be a promising, long-lasting therapeutic strategy for refractory and recurrent uveitis, as well as other inflammatory eye diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways

Qiu

Tao

Zheng

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…These exacerbations of disease may be associated with shifting the response toward M1 macrophages, thereby enhancing the production of proinflammatory cytokines and recruitment of fresh immune cells that exacerbate the disease. Indeed, the symptoms of HSV-induced Bechet disease in mice were ameliorated when the M1/M2 ratio was decreased (97). The roles of M1 and M2 macrophages in protective responses and disease are not universal, however, and may depend on both the disease process and the organism.…”

Section: Discussionmentioning

confidence: 99%

Roles of M1 and M2 Macrophages in Herpes Simplex Virus 1 Infectivity

Lee

Ghiasi

2017

J Virol

View full text Add to dashboard Cite

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-␥) 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-␥ DNA, which enhances the development of M1 macrophages, increased virus replication in the eye; increased latency; and also increased CD4, CD8, IFN-␥, 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-␥,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.KEYWORDS macrophages, infectivity, latency, exhaustion, HSV-1, CSF-1, IFN-␥, polarized, primary infection, reactivation M acrophage infiltrates play key roles in the immune defense system and are a central component of the innate immune system (1-4). Macrophages exhibit a wide variety of critically important functions, including phagocytosis, cytokine/chemokine secretion, and tumor cytotoxicity (5, 6). Resident macrophages are not detectable in the corneas of naive mice (7, 8), and we have confirmed the lack of resident macrophages in the corneas of uninfected mice by immunostaining using anti-F4/80, as well as anti-CD11b, antib...

show abstract

“…Recent studies have shown that IL‐6 and IL‐17 play a central role in the pathogenic process of BD, and their increased levels may represent disease activity markers . According to the literature, IL‐6 and IL‐17 are upregulated in PBMC, skin lesions and serum of patients with BD, which suggests a positive correlation with disease activity .…”

Section: Discussionmentioning

confidence: 99%

“…Behçet disease (BD) is a chronic, multisystem vasculitis, characterized by recurrent aphthous and genital ulcers, ocular and cutaneous lesions, and, occasionally, by articular, vascular, gastrointestinal and neurological involvement . The pathogenesis of BD involves hyperactivity of neutrophils, activation of macrophages and impaired function of vascular cells with endothelial injury . Recent studies have shown that several inflammatory cytokines, such as interleukin (IL)‐6 and IL‐17, are upregulated in peripheral blood mononuclear cells (PBMC) and are elevated in the serum of patients with active BD .…”

mentioning

confidence: 99%