Fucosylated glycans of Taenia crassiceps polarize immune responses towards Th-1 type via toll like receptor [TLR] signaling and interferon-gamma production

The role of the macrophage vis-a-vis NK/T cells in determining the outcome of an immune response to a pathogen, whether Th-1 or Th-2, constitutes a fundamental issue in immunoregulation. Such knowledge is also of paramount importance in understanding the immunopathology of chronic human diseases like tuberculosis, leishmaniasis, hepatosplenic schistosomiasis, cysticercosis and neurocysticercosis. The conventional hypothesis states that interferon gamma [IFN-gamma] produced by T-cells and NK cells, in response to interleukin-12 [IL-12] from macrophages directs the immune response towards a Th-1 type, while IL-4, IL-5 and IL-10 result in a Th-2 type, upon antigen presentation with the necessary co-stimulatory molecules. In this report, we provide evidence that parasite glycans induce IFN-gamma and interleukin-6 [IL-6] production in na‹ve murine spleen cells, via toll like receptor [TLR] activation, possibly from macrophages. The IFN-gamma response is self-limiting. We propose that the relative balance of IFN-gamma and IL-6 determines the total immune response, whether Th-1, Th-1/Th-2 or Th-2 biased. Prolonged stimulation of macrophages by parasite glycans via TLRs down regulates the macrophage IFN-gamma response resulting an IL-6 dominated Th-2 environment. This is an adaptation by the parasite to down regulate the early parasite restrictive Th-1 response to a late parasite permissive Th-2 response during the course of infection. It is proposed that in parasitic helminth infections, the generation of either a Th-1 or a Th-2 response is determined at least in part at the macrophage level, prior to the involvement of NK/T cells and occurs when macrophages first encounter pathogen specific molecules via TLRs

Fucosylated glycans of Taenia crassiceps polarize immune responses towards Th-1 type via toll like receptor [TLR] signaling and interferon-gamma production

The role of the macrophage vis-a-vis NK/T cells in determining the outcome of an immune response to a pathogen, whether Th-1 or Th-2, constitutes a fundamental issue in immunoregulation. Such knowledge is also of paramount importance in understanding the immunopathology of chronic human diseases like tuberculosis, leishmaniasis, hepatosplenic schistosomiasis, cysticercosis and neurocysticercosis. The conventional hypothesis states that interferon gamma [IFN-gamma] produced by T cells and NK cells, in response to interleukin-12 [IL-12,] from macrophages directs the immune response towards a Th-1 type, while IL-4, IL-5 and IL-10 result in a Th-2 type, upon antigen presentation with the necessary co-stimulatory molecules. In this report, we provide evidence that parasite glycans induce IFN-gamma and interleukin-6 [IL-6] production in na‹ve murine spleen cells, via toll like receptor [TLR] activation, possibly from macrophages. The JFN-gamma response is self limiting. We propose that the relative balance of IFN-gamma and IL-6 determines the total immune response, whether Th-1, Th-1/Th-2 or Th-2 biased. Prolonged stimulation of macrophages by parasite glycans via TLRs down regulates the macrophage IFN-gamma response resulting an IL-6 dominated Th-2 environment. This is an adaptation by the parasite to down regulate the early parasite restrictive Th-1 response to a late parasite permissive Th-2 response during the course of infection. It is proposed that in parasitic helminth infections, the generation of either a Th-1 or a Th-2 response is determined at least in part at the macrophage level, prior to the involvement of NK/T cells and occurs when macrophages first encounter pathogen specific molecules via TLRs

Mycobacterium tuberculosis in the A1 Ain Medical District - Epidemiological and DNA evidence for indigenous strains

Oil rich Arabian Gulf countries, including the United Arab Emirates [UAE], have unique population demographics, where expatriate workers represent the majority [>60% in the UAE]. Tuberculosis transmission in these countries is attributed to this influx of foreign labour, especially from neighboring tuberculosis endemic countries, and control measures aim largely at eliminating this foreign source. However, this has not resulted in an elimination of transmission. We have used two, IS 6110 insertion element based, PCR-DNA analysis systems to identify patterns of transmission among citizen and expatriate patients in the UAE. In PCR system 1, intervening DNA sequences between the PGRS repeat and IS6110 was used. In the second, IS6110 was analyzed with respect to the ipl locus [EMBL X59799]. Conventional restriction fragment length polymorphism analysis was also used. Our data show that M. tuberculosis strains isolated from UAE citizen patients were different from those of expatriate workers. We conclude that the primary source of infection in UAE citizen tuberculosis patients in not the expatriate workers, but M. tuberculosis strains indigenous to the region