Subcapsular sinus macrophages limit acute gammaherpesvirus dissemination

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Lymphocytes are key targets for viral infections.
• Myeloid cells, including subcapsular sinus macrophages (SSMs), are crucial for antigen presentation and immune defense.
• The interaction between SSMs and B-cell-tropic viruses remains largely unexplored.

Purpose of the Study:

• To investigate the role of SSMs in the initial encounter with murid herpesvirus-4 (MuHV-4).
• To determine how SSMs influence B-cell infection and viral dissemination.
• To elucidate the mechanism by which SSMs control viral spread.

Main Methods:

• Analysis of MuHV-4 infection in lymph nodes.
• Experimental depletion of SSMs using clodronate-loaded liposomes and diphtheria toxin in transgenic mice.
• Assessment of B-cell infection and viral spread to the spleen.

Main Results:

• MuHV-4 readily infected SSMs, but this infection was poorly productive.
• SSM depletion led to increased B-cell infection and accelerated virus spread to the spleen.
• Dendritic cells were identified as a primary route for B-cell infection.

Conclusions:

• SSMs act as a critical early defense mechanism by non-productively trapping virions from afferent lymph.
• SSMs slow down host colonization by MuHV-4, thereby limiting initial viral spread.
• Targeting SSMs could potentially enhance viral dissemination, underscoring their importance in controlling viral infections.