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Journal of Venomous Animals and Toxins including Tropical Diseases

On-line version ISSN 1678-9199

J. Venom. Anim. Toxins incl. Trop. Dis vol.10 no.3 Botucatu  2004

http://dx.doi.org/10.1590/S1678-91992004000300010 

THESIS

 

Immune response to infection by Leptospira interrogans serovar icterohaemorrhagiae in genetically selected mice

 

 

M. Marinho

Correspondence

 

 

THESIS: M. Marinho submitted this thesis for her Doctorate in Tropical Diseases at Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil, 2000. 

Advisor: Professor Hélio Langoni

ABSTRACT

Leptospirosis has been studied for a long time and its etiology, epidemiology, and pathology are well understood. However, little is known about the host immune response to infection, especially cell-mediated immunity.
This study evaluated cellular and humoral immune response in genetically selected mice strains and BALB/c mice inoculated with Leptospira interrogans serovar icterohaemorrhagiae. The mice were selected as High (H) and Low (L) antibody producers against complex natural antigens (selection IV-A). Strains HIV-A and LIV-A presented changes in some immune response behaviors, mainly related to macrophage activity. These strains showed characteristics of polar phenotypes found in natural heterogeneous populations.
Production of oxygen (H2O2) and nitrogen (NO) intermediate reactives, blastic transformation, INF-g, TNF, and interleukin 4 and 6 were assayed to determine cellular immune response. Antibody titers, Leptospira recovery, and histopathological examination of organs were performed at eight different moments post-infection.
Humoral and cellular response of the different strains were compared to establish distinct immunological profiles. Results showed that after the seventh day of inoculation, the H mouse strain had significantly increased antibody titers than the L mouse strain, thus maintaining the multi-specific effect. The BALB/c mice presented intermediary results between the two strains. The main result was that antibody production played a limitating role in the infection because Leptospira recovery was higher in the initial infection phase when antibody titers were low but increasing. Lesions observed in the organs of infected mice were of degenerative inflammatory process with no other changes over time. The degree of tissue involvement varied according to strain.
HIV-A presented more extensive lesions than the others. Despite the low H2O2 production, the amount was sufficient to stop infection in LIV-A. There was high in vitro NO production in infected animal cells after INF treatment, suggesting that infection primed cytokine stimulated macrophages to produce this metabolite. TNF level remained high and stable throughout bacterial recovery; this could be related to infection pathogenesis.
In general, the HIV-A and BALB/c strains demonstrated a Th2 response pattern, with higher antibody titers, higher IL-4 levels, and severe lesions, while the LIV-A presented a Th1 pattern with higher INF production, macrophage activity, and lower tissue lesion involvement. Other protocols must be performed to confirm these data, mainly immunohistochemistry tests that could be useful to detect cytokines and their involvement in lesions.

Key words: Leptospira interrogans serovar icterrohaemorrhagiae; experiments infection; macrophages, lymphocyte; cytokines; genetically selected mice H, L and BALB/c.

 

 

Correspondence to
Prof. Dr. Hélio Langoni
Núcleo de Pesquisa em Zoonoses (NUPEZO), Departamento de Higiene Veterinária
Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista (UNESP)
Distrito Rubião Junior, s/n, 18618-000, Botucatu, SP, Brasil
E-mail: hlangoni@fmvz.unesp.br

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