Resistance of mice to Leptospira infection and correlation with chemokine response

[Display omitted] •Host-pathogen interaction during Leptospira infection induces expression of chemokines.•Chemokine profiles reflect susceptibility to leptospirosis and are associated to TLR4.•Leptospira transcripts sph1 and tlyA, are upregulated in lungs of susceptible mice in early stages of infe...

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Published in:	Immunobiology (1979) Vol. 222; no. 11; pp. 1004 - 1013
Main Authors:	Domingos, R.H., Pavanel, E.B., Nakajima, E., Schons-Fonseca, L., Da Costa, R.M.A., De Franco, M., Carvalho, E., Ho, P.L., Martins, E.A., Da Silva, J.B.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier GmbH 01-11-2017
Subjects:	Animals Bacterial Proteins - genetics Bacterial Proteins - metabolism C3H/HeJ mice Cells, Cultured Chemokines Chemokines - metabolism Disease Progression Gene Expression Regulation, Bacterial Hemolysin Proteins - genetics Hemolysin Proteins - metabolism Host-Pathogen Interactions Immunity, Innate Inflammation Mediators - metabolism Leptospira - immunology Leptospira infection Leptospirosis - immunology Leptospirosis - pathology Lung - microbiology Lung - physiology Mice Mice, Inbred BALB C Mice, Inbred C3H Microfilament Proteins - genetics Microfilament Proteins - metabolism Pathogen-host interaction Toll-Like Receptor 4 - metabolism Leptospira infection Pathogen-host interaction C3H/HeJ mice Chemokines
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Summary:	[Display omitted] •Host-pathogen interaction during Leptospira infection induces expression of chemokines.•Chemokine profiles reflect susceptibility to leptospirosis and are associated to TLR4.•Leptospira transcripts sph1 and tlyA, are upregulated in lungs of susceptible mice in early stages of infection and repressed in resistant mice.•Inflammatory mediators in leptospirosis are molecular markers of host-pathogen interactions, correlating with the progression of the disease. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0171-2985 1878-3279
DOI:	10.1016/j.imbio.2017.05.017