Macrophages From Latently Infected Mice Have Trained Immunity to HSV-1.

Area of Science:

• Immunology
• Virology
• Epigenetics

Background:

• Macrophages are critical in herpes simplex virus 1 (HSV-1) primary and latent infections.
• Previous research indicates macrophages' significant role in HSV-1 pathogenesis.

Purpose of the Study:

• To investigate if HSV-1 exposure induces lasting functional and epigenetic changes in macrophages.
• To determine if these changes align with trained immunity, enhancing responses to secondary stimulation.

Main Methods:

• Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) on macrophages from latently infected mice.
• Flow cytometry analysis of macrophages in spleen, bone marrow (BM), cornea, and trigeminal ganglia (TG).
• Assessment of responses following secondary HSV-1 infection to evaluate training durability.

Main Results:

• Elevated immunity-related GTPase family M protein (IRGM1) expression in stimulated macrophages from latently infected mice.
• Higher proportion of IRGM1+ macrophages observed in spleen, BM, cornea, and TG of latently infected mice.
• Sustained elevated IRGM1 expression in macrophages from spleen, TG, and BM of latently infected mice.

Conclusions:

• Macrophages develop durable trained immunity against HSV-1 infection.
• IRGM1 is identified as a key factor in maintaining long-term macrophage immunological memory.