The host immune response to parasitic infections plays an important role in controlling multiplication of the parasite and reducing clinical symptoms and life-threatening complications. Nitric oxide (NO), an important innate immune factor and classic Th1 immune effector, may play a role in inhibiting plasmodium infection. In this study, we used two different approaches (L-Arginine [precursor of NO] and NOC5 [short-time NO donor]) to prove the roles of NO in malaria infection. We used 6-8 week-old female BALB/c mice infected with the rodent malaria Plasmodium yoelii Landau, Michel et Adam, 1968 - strain 17XL (P.y17XL) as a model. For L-Arg treatment, mice were administered with an oral dose of 1.5 mg/g L-Arg daily for seven consecutive days prior to infection with Py17XL. L-Arg pretreatment resulted in the decrease of the mRNA level of the apical membrane antigen 1 (AMA1) gene, which encodes a protein involved in host invasion. For NOC5 treatment, NOC5 was injected intraperitoneally into the P.y17XL infected mice on day 5 post-infection or incubated in vitro with purified Py17XL schizonts. Both in vivo and in vitro treatments with NOC5 led to down-regulation of the transcript and protein levels of invasion-related molecules (AMA1, merozoites surface protein 1 and Py235). Our results confirmed the protective role of NO in the asexual blood stage of parasitic infection, which may be partially due to reduced expression of parasite invasion molecules.
- MeSH
- arginin chemie farmakologie MeSH
- hydraziny chemie farmakologie MeSH
- kvantitativní polymerázová řetězová reakce metody MeSH
- malárie imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- oxid dusnatý chemie MeSH
- Plasmodium yoelii fyziologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí metody MeSH
- regulace genové exprese účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In cases of human malaria, children suffer very high rates of morbidity and mortality. To analyse the mechanisms involved in age-dependent protection against malaria, we investigated the characterization of immune responses to Plasmodium yoelii 17XNL (P.y 17XNL) in young (3 weeks) and middle-aged (8 months) C57BL/6 mice. In this study, we found that 100% of young mice succumbed to P.y 17XNL infection with higher parasitemia, while middle-aged mice were able to clear blood parasites and no mortality was observed. These observations suggested that the young C57BL/6 mice were susceptible to P.y 17XNL infection, whereas the middle-aged mice were resistant. Cellular analysis revealed that both the numbers of splenic myeloid dendritic cells (mDCs) as well as the expression of DC maturation markers were higher in middle-aged mice than those in young mice. The numbers of IgG1- or IgG2a-secreting B cells increased markedly in middle-aged mice after infection with P.y 17XNL. The dynamic change of the number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in mice infected with P.y 17XNL was also different between the two groups. In addition, the levels of IFN-gamma and NO increased in both groups during early parasite infection, while there was also an obvious increase in IL-4 production in the infected middle-aged mice. The change in IL-10 levels following infection was consistent with that of the change in the number of Tregs. The survival of middle-aged mice following P.y 17XNL infection was dependent upon the establishment of effective Thl and Th2 responses and a successful switch between Th1 and Th2 responses, as well as appropriate functioning of Tregs.
- MeSH
- B-lymfocyty MeSH
- cytokiny genetika metabolismus MeSH
- imunoglobulin G klasifikace metabolismus MeSH
- interferon gama metabolismus MeSH
- malárie imunologie veterinární MeSH
- myši MeSH
- náchylnost k nemoci imunologie MeSH
- oxid dusnatý metabolismus MeSH
- parazitemie MeSH
- Plasmodium yoelii fyziologie MeSH
- regulace genové exprese imunologie MeSH
- slezina cytologie MeSH
- stárnutí fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH