Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection

• Published in: PLoS pathogens 2021-10, Vol.17 (10), p.e1009999-e1009999
• Main Authors: Jaggi, Ujjaldeep, Matundan, Harry H, Yu, Jack, Hirose, Satoshi, Mueller, Mathias, Wormley, Floyd L, Ghiasi, Homayon
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adoptive transfer; Biology and Life Sciences; Bone marrow; Cornea; Cytokine storm; Cytokines; Development and progression; Eye diseases; Eye infections; Genotype & phenotype; Health aspects; Herpes simplex; Herpes viruses; Infections; Infectivity; Inflammation; Latency; Macrophages; Medicine and Health Sciences; Pathology; Physiological aspects; Replication; Research and Analysis Methods; Rodents; Viruses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1009999

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.