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Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
Resistance of mice to Leptospira infection and correlation with chemokine response
R H Domingos1, E B Pavanel1, E Nakajima1
1Centro de Biotecnologia, Instituto Butantan, São Paulo, 05503-900, Brazil.
Abstract:
Leptospirosis is globally widespread neglected disease, affecting most mammalian species. Clinical signs can be confused with other diseases which make the diagnosis and treatment difficult. Chemokines and cytokines are known for their role in the inflammatory and immune response to infections. The profile determination of chemokines' expressions in the course of infection may elucidate the defense mechanisms of the host and support the search for effective treatment strategies. We investigated the mechanisms of innate immunity through the comparison of chemokines induced during infection with L. interrogans in mice with different levels of susceptibility. We used lung and spleen tissues samples of mice from C3H/HeJ, C3H/HePas and Balb/c, respectively sensitive, intermediate susceptibility and resistant to the pathogen. The inoculation of L. interrogans in C3H/HeJ mice led a comparatively smaller change in chemokines expression in both spleen and lung tissues. In samples from spleens and lungs of C3H/HePas and Balb/c the higher increases occurred on CXCL9, CXCL16, CXCL5, CCL8 and CCL5 in Balb/c. Given the same genetic background, the differences in the responses of C3H/HePas compared to C3H/HeJ mice strongly suggest the role of chemokines for the survival of parental strain. Therefore, the greatest increase in CXC chemokines appears to be efficient to induce migration of cells to the secondary lymphoid organs and affected tissues, which is important to control infection. Overall, CXC chemokines are important for the activation and attraction of T cell and may influence the course and control of the infection in resistant Balb/c mice.
Insights
Leptospirosis infection impacts host defense. Increased CXC chemokines in resistant mice correlate with better control of Leptospira interrogans, suggesting their role in T cell attraction and infection management.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Leptospirosis is a widespread neglected zoonotic disease with varied clinical signs, complicating diagnosis and treatment.
- Chemokines and cytokines are crucial mediators of immune and inflammatory responses during infections.
- Understanding chemokine expression profiles can reveal host defense mechanisms against Leptospira interrogans.
Purpose of the Study:
- To investigate innate immune mechanisms by comparing chemokine induction during L. interrogans infection in mice with varying susceptibility.
- To elucidate the role of specific chemokines in host response and survival.
Main Methods:
- Comparative analysis of chemokine expression in lung and spleen tissues of C3H/HeJ (sensitive), C3H/HePas (intermediate), and Balb/c (resistant) mice infected with L. interrogans.
- Quantitative assessment of chemokine profiles to identify differential responses.
Main Results:
- Infection of susceptible C3H/HeJ mice showed minimal changes in chemokine expression in lung and spleen.
- Resistant Balb/c and intermediate C3H/HePas mice exhibited significant increases in chemokines, notably CXCL9, CXCL16, CXCL5, CCL8, and CCL5 in Balb/c.
- Differences in response between C3H/HePas and C3H/HeJ suggest a role for chemokines in host survival.
Conclusions:
- Elevated CXC chemokine levels are associated with effective control of L. interrogans infection.
- CXC chemokines are vital for attracting immune cells, particularly T cells, to infected tissues and secondary lymphoid organs.
- These findings highlight the importance of CXC chemokines in managing leptospirosis, especially in resistant hosts.

