Thus, loss of PERK signaling might influence downstream genetic and/or epigenetic changes favoring hyper-proliferative disorders characteristic of early steps of breast cancer progression. Pathogenic bacteria use a variety of virulence factors that endow them with the ability to overcome the Oxysophocarpine immune system. Adhesins, enzymes and toxins acting on host tissues, cells and free molecules enable pathogens to breach host barriers and thwart defenses. In most cases, however, the aggression is quickly sensed by innate immune defenses that both act immediately and bolster the adaptive immune response. Innate immunity detects minute amounts of components bearing the so-called pathogen-associated molecular patterns as well as some products of host damage. The subsequent proinflammatory responses are manifestations of the innate immunity and usual landmarks of infection and septic syndromes. However, there is increasing evidence that some pathogens display altered PAMPs in key molecules, suggesting that to escape detection by innate immunity is a survival strategy. We have evaluated the degree and profiles of the early proinflammatory responses induced by B. abortus and several PAMP-bearing molecules in comparison with those evoked by the intracellular pathogen S. typhimurium. This comparative approach allowed us to estimate the level at which Brucella is able to activate innate immunity 
at the onset of the infection. It is important to note that the data obtained accurately correlate with the absence of endotoxicity signs, the rarity of leucocytosis and neutrophilia and the almost total absence of coagulopathies in patients with brucellosis. Therefore, our observations are complementary to a significant body of clinical data. The picture that emerges from this study is as follows. After invading, the brucellae come in contact with humoral mediators and are readily ingested by PMN and macrophages, and probably by dendritic cells. At this stage, Brucella performs several tasks to avoid immediate destruction: first, it circumvents strong activation of the innate immune system; second, the bacterium withstands the direct action of complement and other bactericidal substances; third, it resists and evades the action of professional phagocytes, such as PMN and macrophages; finally, Brucella maintains the host cells alive in order to establish long lasting infections. The first task is accomplished through a negligible induction of proactive plasma inducers of inflammation, insignificant levels of complement fixation and delayed and low levels of cytokines and chemokines, as demonstrated here and in other works. These effects should be connected to the low recruitment of leukocytes at early times and the weak brucellacidal action of PMN. Despite these low-activating properties of Brucella, it was striking that the course of infection was unaffected in mice depleted of granulocytes because PMN kill these bacteria at significant higher rates than macrophages. The brucellacidal activity of PMN is promoted by opsonization with normal sera but it seems that the negligible complement binding displayed by B. abortus which is related to the poor complement binding of its LPS would be a limiting factor. It is noteworthy that the lack of role of PMN parallels that of NK cells in the sense that they are not crucial for the control of B. abortus at early times of infection, at least in the murine model. A possible general consequence of these observations is that PMN, the Diperodon foremost cells of innate immunity, may serve as carriers spreading viable B. abortus in the body as proposed by Spink more than 50 years ago.