ArticlePLoS pathogens2021
Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 26 citations in OpenAlex.
- HSV-1 metabolic hijacking: Mechanisms to precision therapeutics.Virulence · 2026Review
- HSV-1 LAT promotes ocular diseases in the absence of type I IFN responses in sensory neurons.Journal of virology · 2026Article
- Epigenetic profiling reveals M1 macrophages as the primary drivers of trained immunity in HSV-1 latently infected mice.PLoS pathogens · 2026Article
- IL-33-Driven Macrophage Reprogramming as a Potential Immunometabolic Strategy for Herpes Simplex Keratitis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Molecular Pathways Driving Corneal Neovascularization in Herpes Simplex Keratitis.Pathogens (Basel, Switzerland) · 2026Review
- Macrophages From Latently Infected Mice Have Trained Immunity to HSV-1.Investigative ophthalmology & visual science · 2026Article
- CD163+ perivascular macrophages in schizophrenia: a research framework for testing macrophage-related mechanisms.Frontiers in psychiatry · 2026Article
- Divergent roles of macrophage subsets, FoxP3, and IL-17A in HSV-1-induced CNS pathology.PLoS pathogens · 2025Article
- Cyclic GMP-AMP Synthase (cGAS) Deletion Promotes Less Prominent Inflammatory Macrophages and Sepsis Severity in Catheter-Induced Infection and LPS Injection Models.International journal of molecular sciences · 2025Article
- Redefining our vision: an updated guide to the ocular immune system.Nature reviews. Immunology · 2024Review
- The importance of IFNα2A (Roferon-A) in HSV-1 latency and T cell exhaustion in ocularly infected mice.PLoS pathogens · 2024Article
- The immunobiology of corneal HSV-1 infection and herpetic stromal keratitis.Clinical microbiology reviews · 2024Review
- Presence of CD80 and Absence of LAT in Modulating Cellular Infiltration and HSV-1 Latency.Viruses · 2024Article
- Meeting the Challenge of Controlling Viral Immunopathology.International journal of molecular sciences · 2024Review
- Herpes simplex keratitis: A brief clinical overview.World journal of virology · 2024Review
- Absence of CD80 reduces HSV-1 replication in the eye and delays reactivation but not latency levels.Journal of virology · 2024Article
- Article
- The Host-Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment.Microorganisms · 2023Review
- Role of Innate Interferon Responses at the Ocular Surface in Herpes Simplex Virus-1-Induced Herpetic Stromal Keratitis.Pathogens (Basel, Switzerland) · 2023Review
- Controlling viral inflammatory lesions by rebalancing immune response patterns.Frontiers in immunology · 2023Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Ocular HSV-1 infection is a major cause of eye disease and innate and adaptive immunity both play a role in protection and pathology associated with ocular infection. Previously we have shown that M1-type macrophages are the major and earliest infiltrates into the cornea of infected mice. We also showed that HSV-1 infectivity in the presence and absence of M2-macrophages was similar to wild-type (WT) control mice. However, it is not clear whether the absence of M1 macrophages plays a role in protection and disease in HSV-1 infected mice. To explore the role of M1 macrophages in HSV-1 infection, we used mice lacking M1 activation (M1-/- mice). Our results showed that macrophages from M1-/- mice were more susceptible to HSV-1 infection in vitro than were macrophages from WT mice. M1-/- mice were highly susceptible to ocular infection with virulent HSV-1 strain McKrae, while WT mice were refractory to infection. In addition, M1-/- mice had higher virus titers in the eyes than did WT mice. Adoptive transfer of M1 macrophages from WT mice to M1-/- mice reduced death and rescued virus replication in the eyes of infected mice. Infection of M1-/- mice with avirulent HSV-1 strain KOS also increased ocular virus replication and eye disease but did not affect latency-reactivation seen in WT control mice. Severity of virus replication and eye disease correlated with significantly higher inflammatory responses leading to a cytokine storm in the eyes of M1-/- infected mice that was not seen in WT mice. Thus, for the first time, our study illustrates the importance of M1 macrophages specifically in primary HSV-1 infection, eye disease, and survival but not in latency-reactivation.
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