A systemic macrophage response is required to contain a peripheral poxvirus infection
| Autor: | Christopher C. Norbury, Michael L. Davies, Lauren W. Kaminsky, Zia Ur Rahman, Nico van Rooijen, Tracy E. Krouse, Chetna Soni, Irene E. Reider, Matthew A. Fischer, Nikhil J. Parekh |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
viruses Otology Ear Infections Monocytes White Blood Cells Mice 0302 clinical medicine Animal Cells Medicine and Health Sciences Vaccinia Macrophage lcsh:QH301-705.5 Lymph node Animal Models Acquired immune system Flow Cytometry 3. Good health Ovaries medicine.anatomical_structure Infectious Diseases Experimental Organism Systems Lymph Cellular Types Anatomy Research Article lcsh:Immunologic diseases. Allergy Skin Infections Immune Cells Ear infection Immunology Bone Marrow Cells Mouse Models Vaccinia virus Dermatology Biology Research and Analysis Methods Microbiology Virus 03 medical and health sciences Model Organisms Virology Genetics medicine Animals Molecular Biology Innate immune system Blood Cells Monocyte Macrophages Reproductive System Biology and Life Sciences Cell Biology Immunity Innate Mice Inbred C57BL Disease Models Animal 030104 developmental biology lcsh:Biology (General) Otorhinolaryngology Microscopy Fluorescence Ears Parasitology lcsh:RC581-607 Head 030215 immunology |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 13, Iss 6, p e1006435 (2017) |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | 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. Author summary Prior to the eradication of variola virus, the orthopoxvirus that causes smallpox, one-third of infected people succumbed to the disease. Despite many complications, smallpox vaccination using vaccinia virus enabled a successful eradication of the disease. Following smallpox eradication, vaccinia (the smallpox vaccine) remains a widely used vaccine vector, so any information about the immune response to the vector can help engineer safer vaccines, or treatment, following complications of immunization. During natural infection, orthopoxviruses spread from a peripheral site of infection to become systemic. This study elucidates the early requirement of innate immune cells to control spread of the smallpox vaccine vector after a peripheral infection. We report that systemic populations of cells, rather than those recruited to the site of infection, are responsible for preventing virus dissemination. The viral control mediated by these cell subsets presents a potential target for therapies and rational vaccine design. |
| Databáze: | OpenAIRE |
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