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

Michael L. Davies, Nikhil J. Parekh, Lauren W. Kaminsky, Chetna Soni, Irene E. Reider, Tracy E. Krouse, Matthew A. Fischer, Nico van Rooijen, Ziaur Rahman, Christopher Norbury

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere1006435
JournalPLoS Pathogens
Volume13
Issue number6
DOIs
StatePublished - Jan 1 2017

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Poxviridae Infections
Vaccinia virus
Macrophages
Infection
Viruses
Lymph
Lymph Nodes
Virus Diseases
Poxviridae
Skin
Adaptive Immunity
Phagocytes
Dendritic Cells
Monocytes
Immune System
Pathology

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Davies, M. L., Parekh, N. J., Kaminsky, L. W., Soni, C., Reider, I. E., Krouse, T. E., ... Norbury, C. (2017). A systemic macrophage response is required to contain a peripheral poxvirus infection. PLoS Pathogens, 13(6), [e1006435]. https://doi.org/10.1371/journal.ppat.1006435
Davies, Michael L. ; Parekh, Nikhil J. ; Kaminsky, Lauren W. ; Soni, Chetna ; Reider, Irene E. ; Krouse, Tracy E. ; Fischer, Matthew A. ; van Rooijen, Nico ; Rahman, Ziaur ; Norbury, Christopher. / A systemic macrophage response is required to contain a peripheral poxvirus infection. In: PLoS Pathogens. 2017 ; Vol. 13, No. 6.
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Davies, ML, Parekh, NJ, Kaminsky, LW, Soni, C, Reider, IE, Krouse, TE, Fischer, MA, van Rooijen, N, Rahman, Z & Norbury, C 2017, 'A systemic macrophage response is required to contain a peripheral poxvirus infection', PLoS Pathogens, vol. 13, no. 6, e1006435. https://doi.org/10.1371/journal.ppat.1006435

A systemic macrophage response is required to contain a peripheral poxvirus infection. / Davies, Michael L.; Parekh, Nikhil J.; Kaminsky, Lauren W.; Soni, Chetna; Reider, Irene E.; Krouse, Tracy E.; Fischer, Matthew A.; van Rooijen, Nico; Rahman, Ziaur; Norbury, Christopher.

In: PLoS Pathogens, Vol. 13, No. 6, e1006435, 01.01.2017.

Research output: Contribution to journalArticle

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AU - Davies, Michael L.

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Davies ML, Parekh NJ, Kaminsky LW, Soni C, Reider IE, Krouse TE et al. A systemic macrophage response is required to contain a peripheral poxvirus infection. PLoS Pathogens. 2017 Jan 1;13(6). e1006435. https://doi.org/10.1371/journal.ppat.1006435