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Imaging of In Situ Interferon Gamma Production in the Mouse Spleen following Listeria monocytogenes Infection
Published on: July 16, 2019
Il-10 deficient mice express IFN-γ mRNA and clear Leptospira interrogans from their kidneys more rapidly than normal
Amy A Devlin1, Priya J Halvorsen2, Jennifer C Miller3
1Reynolds American, Inc. 401 N. Main St., Winston Salem, NC 27101, United States.
Abstract:
Leptospira interrogans (L. interrogans), the causative agent of leptospirosis, is a widespread zoonotic spirochete that lives a dual lifestyle. L. interrogans infects mice, rats, and wildlife in a persistent and asymptomatic fashion, while also causing productive and acute infections in other mammals such as humans and hamsters. Infections in humans can be fatal, accompanied by a cytokine storm and shock-like symptoms. Production of IL-10 has been noted in both rodent and human infections which has led a number of investigators to hypothesize that IL-10 plays a role in the pathogenesis of this disease. To test this hypothesis we have compared bacteremia and the cytokine response of normal and IL-10 deficient C57Bl/6 mice following ip infection with L. interrogans. In normal mice bacterial 16s mRNA was detected in both lung and kidney tissues within a day after infection. Levels of 16s mRNA then dropped in both organs with complete elimination from the lung by day 3 but persistence in the kidney for 7days after infection. In contrast, in IL-10 deficient mice, the organism was eliminated more rapidly from the kidney. We found that infection of both control and IL-10 deficient mice produced similar levels of a number of pro-inflammatory cytokine mRNAs. On the other hand, IFN-γ mRNA was only induced in IL-10 deficient mice. These results support the hypothesis that L. interrogans ability to induce IL-10, which in turn prevents production of IFN-γ and inhibits T cell immunity, may contribute to the persistent growth of this microorganism in the murine kidney.
Insights
Leptospira interrogans causes leptospirosis. This study shows Interleukin-10 (IL-10) prevents the immune response, allowing persistent bacterial growth in mice kidneys.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Leptospira interrogans causes leptospirosis, a zoonotic disease with varied outcomes in different hosts.
- Interleukin-10 (IL-10) is produced during both rodent and human infections, suggesting a role in disease pathogenesis.
Purpose of the Study:
- To investigate the role of IL-10 in the pathogenesis of Leptospira interrogans infection.
- To compare the course of infection and cytokine response in normal and IL-10 deficient mice.
Main Methods:
- Infection of C57Bl/6 mice (normal and IL-10 deficient) with L. interrogans.
- Quantification of bacterial 16s mRNA in lung and kidney tissues.
- Measurement of pro-inflammatory cytokine and Interferon-gamma (IFN-γ) mRNA levels.
Main Results:
- L. interrogans persisted in the kidneys of normal mice for 7 days, but was cleared more rapidly in IL-10 deficient mice.
- Pro-inflammatory cytokine mRNA levels were similar in both groups.
- IFN-γ mRNA was induced only in IL-10 deficient mice, indicating suppressed T cell immunity in normal mice.
Conclusions:
- Leptospira interrogans induces IL-10, which suppresses IFN-γ production and T cell immunity.
- This IL-10-mediated immune suppression contributes to persistent bacterial growth in the murine kidney.
- Targeting IL-10 may offer a strategy for managing leptospirosis.
