A systemic macrophage response is required to contain a peripheral poxvirus infection

PLoS Pathogens

Nikhil J. Parekh¹  Ziaur S. M. Rahman¹  Irene E. Reider¹  Chetna Soni¹  Michael L. Davies¹  Tracy E. Krouse¹  Matthew A. Fischer¹  Christopher C. Norbury¹  Lauren W. Kaminsky¹  Nico van Rooijen² 

[1] Department of Microbiology and Immunology, College of Medicine, Pennsylvania State University, Hershey, PA, United States of America;Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit, BT Amsterdam, The Netherlands

关键词: Macrophages;    Bone marrow cells;    Skin infections;    Ovaries;    Monocytes;    Ear infections;    Mouse models;    Viral replication;   

DOI  :  10.1371/journal.ppat.1006435

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The goal of the innate immune system is to reduce pathogen spread prior to the initiation of an effective adaptive immune response. Following an infection at a peripheral site, virus typically drains through the lymph to the lymph node prior to entering the blood stream and being systemically disseminated. Therefore, there are three distinct spatial checkpoints at which intervention to prevent systemic spread of virus can occur, namely: 1) the site of infection, 2) the draining lymph node via filtration of lymph or 3) the systemic level via organs that filter the blood. We have previously shown that systemic depletion of phagocytic cells allows viral spread after dermal infection with Vaccinia virus (VACV), which infects naturally through the skin. Here we use multiple depletion methodologies to define both the spatial checkpoint and the identity of the cells that prevent systemic spread of VACV. Subcapsular sinus macrophages of the draining lymph node have been implicated as critical effectors in clearance of lymph borne viruses following peripheral infection. We find that monocyte populations recruited to the site of VACV infection play a critical role in control of local pathogenesis and tissue damage, but do not prevent dissemination of virus. Following infection with virulent VACV, the subcapsular sinus macrophages within the draining lymph node become infected, but are not exclusively required to prevent systemic spread. Rather, small doses of VACV enter the bloodstream and the function of systemic macrophages, but not dendritic cells, is required to prevent further spread. The results illustrate that a systemic innate response to a peripheral virus infection may be required to prevent widespread infection and pathology following infection with virulent viruses, such as poxviruses.

【 授权许可】

CC BY