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Effect of sex steroids on Babesia microti infection in mice.

ABSTRACT: Sex-based-differences are known to affect susceptibility to protozoan infections, but their effects on parasitemia and clinical symptoms in Babesia infections remain unclear. We examined the sex-based susceptibility of various mouse strains to Babesia microti Munich strain infection. In all strains, male mice exhibited significantly higher peak parasitemia and more severe anemia than female mice. Testosterone and estradiol-17? treatment caused an increase in parasitemia and aggravation of anemia. Orchidectomized male mice receiving testosterone exhibited smaller splenic macrophage populations three days after infection, smaller B cell populations 10 days after infection, and reduced splenic tumor necrosis factor-? and interferon-? mRNA expression than mice that did not receive testosterone. Mice receiving estradiol-17? did not exhibit immunosuppressive effects. Thus, a weakened and delayed innate immunity response may lead to acquired immunity failure. The results suggested that testosterone directly affects T or B cells, leading to delayed acquired immunity, dramatically increased parasitemia, and severe anemia.

SUBMITTER: Sasaki M

PROVIDER: S-EPMC3583332 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Effect of sex steroids on Babesia microti infection in mice.

Sasaki Mizuki M Fujii Yoshito Y Iwamoto Maya M Ikadai Hiromi H

The American journal of tropical medicine and hygiene 20121218 2

Sex-based-differences are known to affect susceptibility to protozoan infections, but their effects on parasitemia and clinical symptoms in Babesia infections remain unclear. We examined the sex-based susceptibility of various mouse strains to Babesia microti Munich strain infection. In all strains, male mice exhibited significantly higher peak parasitemia and more severe anemia than female mice. Testosterone and estradiol-17β treatment caused an increase in parasitemia and aggravation of anemia ...[more]

PMID: 23249689

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Project description:BackgroundBabesiosis is caused by the invasion of erythrocytes by parasites of the Babesia spp. Babesia microti is one of the primary causative agents of human babesiosis. To better understand the status of the disease, discovering key biomarkers of the different infection stages is crucial.ResultsThis study investigated B. microti infection in the mouse model from 0 to 270 days post-infection (dpi), using blood smears, PCR assays and ELISA. PCR assays showed a higher sensitivity when compared to microscopic examination. Specific IgG antibodies could be detected from 7 days to 270 dpi. Two-dimensional electrophoresis was combined with western blotting and mass spectrometric analysis to screen for specific reactive antigens during both the peak parasitaemia period (7 dpi) and IgG antibody response peak period (30 dpi) by the infected mice plasma. The 87 positive reactive proteins were identified and then expressed with the wheat germ cell-free system. Protein microarrays of all 87 targeted proteins were produced and hybridized with the serial plasma of infected mice model. Based on the antigen reaction profile during the infection procedure, 6 antigens were selected and expressed in Escherichia coli. Due to an early response to IgM, lower immunoreactivity levels of IgG after two months and higher immunoreactivity level IgG during nine months, four recombinant proteins were selected for further characterization, namely rBm2D97(CCF75281.1), rBm2D33(CCF74637.1), rBm2D41(CCF75408.1) and rBm7(CCF73510.1). The diagnostic efficacy of the four recombinant protein candidates was evaluated in a clinical setting using babesiosis patient plasma. The rBm2D33 showed the highest sensitivity with a positive rate of 62.5%. Additional characterization of the two candidate proteins using a mouse vaccination assay, demonstrated that rBm2D41 could reduce peak parasitaemia by 37.4%, indicating its efficacy in preventing severe babesiosis.ConclusionsThe detection technologies of microscopic examination, PCR assays and antibody tests showed different sensitivities and accuracy during the different stages of B. microti infection. Antibody detection has a unique significance for B. microti infection in the asymptomatic stages. Using immunoreactivity profiles, biomarkers for disease progression were identified and represent useful information for future the diagnosis and vaccine development for this serious disease of public health significance.

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Effect of sex steroids on Babesia microti infection in mice.

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Effect of sex steroids on Babesia microti infection in mice.

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