{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:58:04Z","timestamp":1791269884274,"version":"4.1.0"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T00:00:00Z","timestamp":1377561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The majority of human<jats:named-content content-type=\"genus-species\">Yersinia pestis<\/jats:named-content>infections result from introduction of bacteria into the skin by the bite of an infected flea. Once in the dermis,<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>can evade the host\u2019s innate immune response and subsequently disseminate to the draining lymph node (dLN). There, the pathogen replicates to large numbers, causing the pathognomonic bubo of bubonic plague. In this study, several cytometric and microscopic techniques were used to characterize the early host response to intradermal (i.d.)<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>infection. Mice were infected i.d. with fully virulent or attenuated strains of dsRed-expressing<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>, and tissues were analyzed by flow cytometry. By 4\u00a0h postinfection, there were large numbers of neutrophils in the infected dermis and the majority of cell-associated bacteria were associated with neutrophils. We observed a significant effect of the virulence plasmid (pCD1) on bacterial survival and neutrophil activation in the dermis. Intravital microscopy of i.d.<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>infection revealed dynamic interactions between recruited neutrophils and bacteria. In contrast, very few bacteria interacted with dendritic cells (DCs), indicating that this cell type may not play a major role early in<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>infection. Experiments using neutrophil depletion and a CCR7 knockout mouse suggest that dissemination of<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>from the dermis to the dLN is not dependent on neutrophils or DCs. Taken together, the results of this study show a very rapid, robust neutrophil response to<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>in the dermis and that the virulence plasmid pCD1 is important for the evasion of this response.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold><jats:named-content content-type=\"genus-species\">Yersinia pestis<\/jats:named-content>remains a public health concern today because of sporadic plague outbreaks that occur throughout the world and the potential for its illegitimate use as a bioterrorism weapon. Since bubonic plague pathogenesis is initiated by the introduction of<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>into the skin, we sought to characterize the response of the host\u2019s innate immune cells to bacteria early after intradermal infection. We found that neutrophils, innate immune cells that engulf and destroy microbes, are rapidly recruited to the injection site, irrespective of strain virulence, indicating that<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>is unable to subvert neutrophil recruitment to the site of infection. However, we saw a decreased activation of neutrophils that were associated with<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>strains harboring the pCD1 plasmid, which is essential for virulence. These findings indicate a role for pCD1-encoded factors in suppressing the activation\/stimulation of these cells<jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/mbio.00170-13","type":"journal-article","created":{"date-parts":[[2013,8,28]],"date-time":"2013-08-28T02:02:03Z","timestamp":1377655323000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":59,"title":["Yersinia pestis Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague"],"prefix":"10.1128","volume":"4","author":[{"given":"Jeffrey G.","family":"Shannon","sequence":"first","affiliation":[{"name":"Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Hasenkrug","sequence":"additional","affiliation":[{"name":"Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Dorward","sequence":"additional","affiliation":[{"name":"Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Nair","sequence":"additional","affiliation":[{"name":"Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron B.","family":"Carmody","sequence":"additional","affiliation":[{"name":"Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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