<named-content content-type="genus-species">Yersinia pestis</named-content> Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague
ABSTRACT The majority of human Yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. Once in the dermis, Y. pestis can evade the host’s innate immune response and subsequently disseminate to the draining lymph node (dLN). There, the pathogen r...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2013-11-01
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| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00170-13 |
| _version_ | 1819038286807564288 |
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| author | Jeffrey G. Shannon Aaron M. Hasenkrug David W. Dorward Vinod Nair Aaron B. Carmody B. Joseph Hinnebusch |
| author_facet | Jeffrey G. Shannon Aaron M. Hasenkrug David W. Dorward Vinod Nair Aaron B. Carmody B. Joseph Hinnebusch |
| author_sort | Jeffrey G. Shannon |
| collection | DOAJ |
| description | ABSTRACT The majority of human Yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. Once in the dermis, Y. pestis can evade the host’s 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.) Y. pestis infection. Mice were infected i.d. with fully virulent or attenuated strains of dsRed-expressing Y. pestis, and tissues were analyzed by flow cytometry. By 4 h 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. Y. pestis 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 Y. pestis infection. Experiments using neutrophil depletion and a CCR7 knockout mouse suggest that dissemination of Y. pestis 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 Y. pestis in the dermis and that the virulence plasmid pCD1 is important for the evasion of this response. IMPORTANCE Yersinia pestis 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 Y. pestis into the skin, we sought to characterize the response of the host’s 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 Y. pestis is unable to subvert neutrophil recruitment to the site of infection. However, we saw a decreased activation of neutrophils that were associated with Y. pestis 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 in vivo. |
| first_indexed | 2024-12-21T08:34:54Z |
| format | Article |
| id | doaj.art-1f2e35ecf3274e0da4d586d39ce847e5 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-21T08:34:54Z |
| publishDate | 2013-11-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-1f2e35ecf3274e0da4d586d39ce847e52022-12-21T19:10:06ZengAmerican Society for MicrobiologymBio2150-75112013-11-014510.1128/mBio.00170-13<named-content content-type="genus-species">Yersinia pestis</named-content> Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic PlagueJeffrey G. Shannon0Aaron M. Hasenkrug1David W. Dorward2Vinod Nair3Aaron B. Carmody4B. Joseph Hinnebusch5Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USALaboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USAResearch Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USAResearch Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USAResearch Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USALaboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USAABSTRACT The majority of human Yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. Once in the dermis, Y. pestis can evade the host’s 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.) Y. pestis infection. Mice were infected i.d. with fully virulent or attenuated strains of dsRed-expressing Y. pestis, and tissues were analyzed by flow cytometry. By 4 h 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. Y. pestis 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 Y. pestis infection. Experiments using neutrophil depletion and a CCR7 knockout mouse suggest that dissemination of Y. pestis 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 Y. pestis in the dermis and that the virulence plasmid pCD1 is important for the evasion of this response. IMPORTANCE Yersinia pestis 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 Y. pestis into the skin, we sought to characterize the response of the host’s 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 Y. pestis is unable to subvert neutrophil recruitment to the site of infection. However, we saw a decreased activation of neutrophils that were associated with Y. pestis 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 in vivo.https://journals.asm.org/doi/10.1128/mBio.00170-13 |
| spellingShingle | Jeffrey G. Shannon Aaron M. Hasenkrug David W. Dorward Vinod Nair Aaron B. Carmody B. Joseph Hinnebusch <named-content content-type="genus-species">Yersinia pestis</named-content> Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague mBio |
| title | <named-content content-type="genus-species">Yersinia pestis</named-content> Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague |
| title_full | <named-content content-type="genus-species">Yersinia pestis</named-content> Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague |
| title_fullStr | <named-content content-type="genus-species">Yersinia pestis</named-content> Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague |
| title_full_unstemmed | <named-content content-type="genus-species">Yersinia pestis</named-content> Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague |
| title_short | <named-content content-type="genus-species">Yersinia pestis</named-content> Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague |
| title_sort | named content content type genus species yersinia pestis named content subverts the dermal neutrophil response in a mouse model of bubonic plague |
| url | https://journals.asm.org/doi/10.1128/mBio.00170-13 |
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