Inflammatory monocytes mediate control of acute alphavirus infection in mice
Publication Date
December 15, 2017
Authors
Kelsey C. Haist, Kristina S. Burrack, Bennett J. Davenport & Thomas E. Morrison
Volume
13
Issue
12
Pages
e1006748
DOI
https://dx.plos.org/10.1371/journal.ppat.1006748
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1006748
Scopus
85039916468
Mendeley
http://www.mendeley.com/research/inflammatory-monocytes-mediate-control-acute-alphavirus-infection-mice
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Mendeley | Further Information

{"title"=>"Inflammatory monocytes mediate control of acute alphavirus infection in mice", "type"=>"journal", "authors"=>[{"first_name"=>"Kelsey C.", "last_name"=>"Haist", "scopus_author_id"=>"56644667500"}, {"first_name"=>"Kristina S.", "last_name"=>"Burrack", "scopus_author_id"=>"56994126300"}, {"first_name"=>"Bennett J.", "last_name"=>"Davenport", "scopus_author_id"=>"36878485400"}, {"first_name"=>"Thomas E.", "last_name"=>"Morrison", "scopus_author_id"=>"7101728102"}], "year"=>2017, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "doi"=>"10.1371/journal.ppat.1006748", "sgr"=>"85039916468", "scopus"=>"2-s2.0-85039916468", "isbn"=>"1111111111", "pmid"=>"29244871", "pui"=>"620067146"}, "id"=>"937d2009-6971-3b4a-aff8-b6687da6740d", "abstract"=>"Chikungunya virus (CHIKV) and Ross River virus (RRV) are mosquito-transmitted alpha- viruses that cause debilitating acute and chronic musculoskeletal disease. Monocytes are implicated in the pathogenesis of these infections; however, their specific roles are not well defined. To investigate the role of inflammatory Ly6ChiCCR2+ monocytes in alphavirus path- ogenesis, we used CCR2-DTR transgenic mice, enabling depletion of these cells by admin- istration of diptheria toxin (DT). DT-treated CCR2-DTR mice displayed more severe disease following CHIKV andRRV infection and had fewer Ly6Chi monocytes and NK cells in circula- tion and muscle tissue compared with DT-treatedWTmice. Furthermore, depletion of CCR2+ or Gr1+ cells, but not NK cells or neutrophils alone, restored virulence and increased viral loads in mice infected with an RRV strain encoding attenuating mutations in nsP1 to levels detected in monocyte-depleted mice infected with fully virulent RRV. Disease severity and viral loads also were increased in DT-treated CCR2-DTR+;Rag1-/- mice infected with the nsP1 mutant virus, confirming that these effects are independent of adaptive immunity. Monocytes and macrophages sorted from muscle tissue of RRV-infected mice were viral RNA positive and had elevated expression of Irf7, and co-culture of Ly6Chi monocytes with RRV-infected cells resulted in induction of type I IFN gene expression in monocytes that was Irf3;Irf7 and Mavs-dependent. Consistent with these data, viral loads of the attenuated nsP1 mutant virus were equivalent to those ofWTRRV in Mavs-/- mice. Finally, reconstitu- tion of Irf3-/-;Irf7-/- mice with CCR2-DTR bone marrow rescued mice from severe infection, and this effect was reversed by depletion of CCR2+ cells, indicating that CCR2+ hematopoi- etic cells are capable of inducing an antiviral response. Collectively, these data suggest that MAVS-dependent production of type I IFN by monocytes is critical for control of acute alpha- virus infection and that determinants in nsP1, the viral RNA capping protein, counteract this response.", "link"=>"http://www.mendeley.com/research/inflammatory-monocytes-mediate-control-acute-alphavirus-infection-mice", "reader_count"=>10, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>1, "Other"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>1, "Other"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>1, "Psychology"=>1, "Immunology and Microbiology"=>5, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>2}

Scopus | Further Information

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