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Updated: Jul 18, 2026
A Non-invasive and Technically Non-intensive Method for Induction and Phenotyping of Experimental Bacterial Pneumonia in Mice
Published on: September 28, 2016
Delayed inflammatory response to primary pneumonic plague occurs in both outbred and inbred mice
Sarah S Bubeck1, Angelene M Cantwell, Peter H Dube
1Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA.
Abstract:
Yersinia pestis is the causative agent of plague, a disease that can manifest as either bubonic or pneumonic plague. An interesting feature of plague is that it is a rapidly progressive disease, suggesting that Y. pestis either evades and/or suppresses the innate immune response to infection. Therefore, the early host response during the course of primary pneumonic plague was investigated in two mouse strains, the outbred strain CD1 and the inbred strain C57BL/6. A comparative analysis of the course of disease in these two strains of mice indicated that they are susceptible to intranasal Y. pestis CO92 infection and have similar 50% lethal doses and kinetics of infection with respect to colonization of the lung, liver, and spleen. Significantly, in both strains of mice, robust neutrophil recruitment to the lungs was not observed until 48 h after infection, suggesting that there was a delay in inflammatory cell recruitment to the site of infection. In addition, proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha, gamma interferon, IL-12p70, monocyte chemoattractant protein 1) and chemokines (KC, MIP-2) in the bronchoalveolar lavage fluids were not readily detected until 48 h after infection, which coincided with the increase in polymorphonuclear leukocyte (PMN) recruitment to the lungs. In comparison, CD1 mice with gram-negative pneumonia caused by Klebsiella pneumoniae exhibited strong inflammatory responses early in infection, with PMNs comprising the majority of the cells in the bronchoalveolar lavage fluid 24 h postinfection, indicating that PMN recruitment to the lungs could occur earlier in this infection than in Y. pestis infection. Together, our results indicate that there is a delay in the recruitment of neutrophils to the lungs in the mouse model of primary plague pneumonia that correlates with delayed expression of proinflammatory cytokines and chemokines in both outbred and inbred mice.
Insights
Yersinia pestis infection delays neutrophil recruitment to the lungs. This delay in immune cell response correlates with suppressed early cytokine and chemokine expression in a mouse model of pneumonic plague.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Yersinia pestis causes plague, a rapidly progressive disease.
- Plague's rapid progression suggests Y. pestis evades or suppresses the innate immune response.
- Understanding the early host response is crucial for combating Y. pestis infections.
Purpose of the Study:
- To investigate the early host immune response during primary pneumonic plague.
- To compare the immune response in two different mouse strains (CD1 and C57BL/6).
- To identify potential delays in inflammatory cell recruitment and cytokine/chemokine expression.
Main Methods:
- Intranasal inoculation of Y. pestis CO92 in CD1 and C57BL/6 mice.
- Comparative analysis of disease progression, including colonization of organs.
- Assessment of bronchoalveolar lavage fluid for inflammatory cells and cytokines/chemokines.
- Comparison with a Klebsiella pneumoniae pneumonia model.
Main Results:
- Both mouse strains showed susceptibility to Y. pestis infection with similar lethal doses and infection kinetics.
- Robust neutrophil recruitment to the lungs was significantly delayed, observed only at 48 hours post-infection.
- Pro-inflammatory cytokines and chemokines were not readily detected until 48 hours post-infection, coinciding with neutrophil influx.
- In contrast, Klebsiella pneumoniae infection induced a strong inflammatory response with early neutrophil recruitment.
Conclusions:
- A significant delay exists in neutrophil recruitment to the lungs during experimental pneumonic plague.
- This delayed immune cell recruitment correlates with delayed expression of key pro-inflammatory mediators.
- The findings suggest Y. pestis actively suppresses or evades early innate immune responses in the lungs.
