Transcriptomic and innate immune responses to Yersinia pestis in the lymph node during bubonic plague.
A delayed inflammatory response is a prominent feature of infection with Yersinia pestis, the agent of bubonic and pneumonic plague. Using a rat model of bubonic plague, we examined lymph node histopathology, transcriptome, and extracellular cytokine levels to broadly characterize the kinetics and extent of the host response to Y. pestis and how it is influenced by the Yersinia virulence plasmid (pYV). Remarkably, dissemination and multiplication of wild-type Y. pestis during the bubonic stage of disease did not induce any detectable gene expression or cytokine response by host lymph node cells in the developing bubo. Only after systemic spread had led to terminal septicemic plague was a transcriptomic response detected, which included upregulation of several cytokine, chemokine, and other immune response genes. Although an initial intracellular phase of Y. pestis infection has been postulated, a Th1-type cytokine response associated with classical activation of macrophages was not observed during the bubonic stage of disease. However, elevated levels of interleukin-17 (IL-17) were present in infected lymph nodes. In the absence of pYV, sustained recruitment to the lymph node of polymorphonuclear leukocytes (PMN, or neutrophils), the major IL-17 effector cells, correlated with clearance of infection. Thus, the ability to counteract a PMN response in the lymph node appears to be a major in vivo function of the Y. pestis virulence plasmid.
Comer
Jason E
JE
Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Sturdevant
Daniel E
DE
Carmody
Aaron B
AB
Virtaneva
Kimmo
K
Gardner
Donald
D
Long
Dan
D
Rosenke
Rebecca
R
Porcella
Stephen F
SF
Hinnebusch
B Joseph
BJ
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D007113:Immunity, Innate / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010930:Plague / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016133:Polymerase Chain Reaction; D051381:Rats; D015010:Yersinia pestis / Q000276:immunology*
D018925:Chemokines; D016207:Cytokines