In contrast, the large Oligomycin A 579-13-5 doses of bacteria effected maximal cytokines release in WT infected pigs. The exagger ated high levels of cytokines perhaps exacerbate the inflammation and were considered to be responsible for S. suis caused diseases. So the successful lethal pathogens could persistently induce cytokines secreted originally to clear the foreign invader, and as a result, the hosts defense was utilized by S. suis to cause dis eases, and to some extent to death. As we all know that the secreted cytokine is an impor tant part of a host defense system, which could recruit inflammatory cells to sites of tissue damage and help to eliminate the pathogens. However, this innate defense system is a double edged sword. If the recruiting inflam matory cells could kill the invader, the disease could be controlled.

On the opposite side, if the recruiting phago cytes could not efficiently kill the bacteria, the tide would be turned to pathogens favor, and the persis tently induced cytokines would result in the exacerbated inflammation and lead to the death during the septic phase of infection. These might be the reason why the survival rate could be elevated when inflammation was inhibited by IL 10, and why the level of cytokine was correlated inversely with survival time in patients with sepsis. In coincidence with our analysis, patho genic S. suis could effectively resist the uptake by phago cytes and CPS could inhibit activation of signaling pathways involved in phagocytosis. In addi tion, several virulence associated proteins such as FBPS, PDGA, LTA, HP0197, serine protease etc.

were also contributed to the phagocytosis resistance, and the up regulation of these proteins in vivo may suggest the better phagocytosis resistance. Due to failing phagocytosis, bac teria could not only cause exacerbated inflammation but also contribute to its survival in the bloodstream in modified Trojan Horse theory in which bacteria travel extracellularly while attached to, but not phagocytosed, and then cause bacteremia and even septemia. One of the key questions to be answered is how S. suis crosses the blood brain barrier to cause meningi tis, which was observed in all WT infected pigs. The findings of the reported study presented that suilysin positive strain could show toxin to produce functional alteration and increase the permeability of BBB, and Sui lysin negative strain might stimulate the production of proinflammatory cytokines resulting in alteration of BBB permeability.

And they also indicated that this highly pathogenic strain could produce high level of tox ins in vivo Suilysin, MRP, hyl, and Dacomitinib undoubtedly it would contribute to the penetration of deep tissue and BBB. In addition, the stimulated production of proin flammatory cytokines would result in the alteration of BBB permeability, and it would be more feasible for S.