Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection
| Autor: | Mathias Mueller, Satoshi Hirose, Jack C. Yu, Ujjaldeep Jaggi, Harry H. Matundan, Homayon Ghiasi, Floyd L. Wormley |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pathology
Adoptive cell transfer Eye Diseases Physiology Herpesvirus 1 Human Cornea White Blood Cells Mice Medical Conditions Animal Cells Immune Physiology Medicine and Health Sciences Biology (General) Infectivity Innate Immune System Animal Models Acquired immune system Virus Latency Experimental Organism Systems Cell Processes Cytokines Cellular Types Anatomy Cytokine Release Syndrome Research Article medicine.medical_specialty QH301-705.5 Phagocytosis Immune Cells Ocular Anatomy Immunology Virulence Mouse Models Biology Research and Analysis Methods Microbiology Virus Model Organisms Ocular System Virology Genetics medicine Animals Molecular Biology Blood Cells Macrophages Biology and Life Sciences Cell Biology RC581-607 Molecular Development medicine.disease eye diseases Viral Replication Ophthalmology Viral replication Immune System Animal Studies Keratitis Herpetic Eyes Parasitology Virus Activation Immunologic diseases. Allergy Cytokine storm Head Developmental Biology |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 17, Iss 10, p e1009999 (2021) |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | 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. Author summary Macrophages circulating in the blood or present in different tissues constitute an important barrier against infection. We previously showed that the absence of M2 macrophages does not impact HSV-1 infectivity in vivo. However, in this study we demonstrated an essential role of M1 macrophages in protection from primary HSV-1 replication, death, and eye disease but not in latency-reactivation. |
| Databáze: | OpenAIRE |
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