Bacillus Calmette-Guérin (BCG) is an attenuated Mycobacterium tuberculosis vaccine. We performed a series of co-infection experiments with BCG-Plasmodium chabaudi chabaudi Landau, 1965 AS using C57BL/6 mice to analyse whether BCG can affect the development of protective immunity to infection with Plasmodium spp. and the mechanism of this protection. We divided mice into four groups: BCG-inoculation 4 weeks prior to P. c. chabaudi AS infection (B-4w-Pc); simultaneous BCG-inoculation and P. c. chabaudi AS infection (Pc+B); BCG-inoculation 3 days post P. c. chabaudi AS (Pc-3-B) infection; and mono-P. c. chabaudi AS infection as control (Pc). The parasitemia level in the B-4w-Pc group was noticeably higher than control group at 6-19 days post infection (dpi). Compared with the control group, the proportion of CD4+CD69+ T cells was significantly reduced 5, 8 and 12 dpi, but the proportion of CD4+CD25+Foxp3+ Tregs was significantly increased in the B-4w-Pc group on 5 and 8 dpi. The B-4w-Pc group also demonstrated reduced levels of IFN-γ and TNF-α on 5 and 8 dpi and significantly elevated level of IL-10 on 12 dpi. There were significantly fewer mDCs (CD11c+CD11b+) and pDCs (CD11c+B220+) in the B-4w-Pc group than the control group at all the time points post infection and the expression of MHC II was noticeably reduced on day 8 pi. Our findings confirmed that BCG inoculation prior to Plasmodium infection resulted in excessive activation and proliferation of Tregs and upregulation of anti-inflammatory mediators, which inhibited establishment of a Th1-dominant immune response during the early stages of Plasmodium infection by inhibiting dendritive cells response. BCG inoculation prior to P. c. chabaudi AS infection may contribute to overgrowth of parasites as well as mortality in mice., Dong-Hua Cao, Ji-Chun Wang, Jun Liu, Yun-Ting Du, Li-Wang Cui, Ya-Ming Cao., and Obsahuje bibliografii
Protective immunity against murine malaria infection depends largely on the establishment of effective Th1 immune response during the early stages of infection. Experimental data suggest that the death of Plasmodium yoelii 17XL (P.y 17XL) susceptible BALB/c mice results from the suppression of Th1 immune response mediated by CD4+CD25+Foxp3+regulatory T cells (Tregs). However, the mechanism by which Tregs regulate Th1 immune response is poorly understood. Since immunity is initiated by dendritic cells (DCs), we analysed DC responses to P.y 17XL in control and Treg-depleted BALB/c mice. Myeloid DC proliferation, phenotypic maturation and interleukin-12 (IL-12) production were strongly inhibited in control BALB/c mice. In contrast, plasmacytoid DC proliferation and IL-10 production were strongly enhanced in control BALB/c mice. In-vivo depletion of Tregs resulted in significantly reversed inhibition of DC response, which may contribute to the establishment of Th1 immune response, indicating that Tregs contribute to the suppression of Th1 immune response during malaria. These findings suggest Tregs contribute to prevent Th1 immune response establishment during the early stage of P.y 17XL infection by inhibiting DC response.
The symmetric implicational method is revealed from a different perspective based upon the restriction theory, which results in a novel fuzzy inference scheme called the symmetric implicational restriction method. Initially, the SIR-principles are put forward, which constitute optimized versions of the triple I restriction inference mechanism. Next, the existential requirements of basic solutions are given. The supremum (or infimum) of its basic solutions is achieved from some properties of fuzzy implications. The conditions are obtained for the supremum to become the maximum (or the infimum to be the minimum). Lastly, four concrete examples are provided, and it is shown that the new method is better than the triple I restriction method, because the former is able to let the inference more compact, and lead to more and superior particular inference schemes.