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Difference in Strain Pathogenicity of Septicemic Yersinia pestis Infection in a TLR2-/- Mouse Model
Kyle L O'Donnell1, Peter L Knopick1, Riley Larsen1
1Department of Biomedical Sciences, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, North Dakota, USA.
Abstract:
Yersinia pestis is the causative agent of bubonic, pneumonic, and septicemic plague. We demonstrate that Toll-like receptor 2-deficient (TLR2-/-) mice are resistant to septicemic infection by the KIM5 strain of Y. pestis but not to infection by the CO92 Δpgm strain. This resistance is dependent on TLR2, the route of infection, and the isoform of YopJ. Elevated bacterial burdens were found in the spleens of CO92 Δpgm-infected animals by 24 h postinfection and in the livers by 4 days. The YopJ isoform present contributed directly to cytotoxicity and inflammatory cytokine production of bone marrow-derived macrophages from TLR2-/- mice. Immune cell trafficking is altered in CO92 Δpgm infections, with an increased neutrophil infiltration to the spleen 5 days postinfection. Immune cell infiltration to the liver was greater and earlier in KIM5-infected TLR2-/- mice. The functionality of the immune cells was assessed by the ability to develop reactive oxygen and nitrogen species. Our data suggest an inhibition of granulocytes in forming these species in CO92 Δpgm-infected TLR2-/- mice. These findings suggest that resistance to KIM5 in TLR2-/- mice is dependent on early immune cell trafficking and functionality.
Insights
Toll-like receptor 2 (TLR2) deficiency confers resistance to Yersinia pestis KIM5 infection in mice, but not to the CO92 Δpgm strain. This resistance depends on TLR2, infection route, and YopJ, impacting immune cell function and trafficking.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Yersinia pestis causes plague, a severe bacterial infection.
- Toll-like receptor 2 (TLR2) plays a role in innate immunity against bacterial pathogens.
Purpose of the Study:
- To investigate the role of TLR2 in Yersinia pestis infection using TLR2-deficient mice.
- To determine the influence of different Yersinia pestis strains and YopJ isoforms on infection outcomes.
Main Methods:
- Comparison of Yersinia pestis infection in wild-type and TLR2-deficient mice.
- Assessment of bacterial burdens, immune cell infiltration, and immune cell functionality (reactive oxygen and nitrogen species production).
- Evaluation of cytotoxicity and cytokine production by macrophages.
Main Results:
- TLR2-deficient mice were resistant to Yersinia pestis KIM5 but susceptible to CO92 Δpgm infection.
- Bacterial burdens were elevated in the spleen and liver of CO92 Δpgm-infected mice.
- YopJ isoform affected macrophage cytotoxicity and cytokine production.
- Immune cell trafficking and granulocyte function were altered in TLR2-deficient mice during infection.
Conclusions:
- TLR2-dependent resistance to Yersinia pestis KIM5 infection involves early immune cell trafficking and functionality.
- The outcome of Yersinia pestis infection in TLR2-deficient mice is strain-specific and influenced by YopJ.
- TLR2 signaling is critical for controlling Yersinia pestis infections, with variations based on bacterial strain and virulence factors.
