MCP-1 is known for its ability to act as potent chemoattractant and activator of monocytes/macrophages as well as NK cells but not neutrophils selleck compound [31, 32] . IP-10 has no chemotactic activity for neutrophils but attracts monocytes, NK, and T cells to the site of infection and regulates T cell maturation [33, 34]. It was reported previously that elevated IL-8 and MCP-1 were secreted by human epithelial cells after Y. enterocolitica infection, but not IP-10 [35, 36]. Human dendritic cells, infected with B. anthracis spores, secreted high level of IL-8 at 7.5 hours [16].

In our study, the fold increase of IL-8 was much greater than MCP-1 and IP-10 (Figure 2). For example, the induction of IL-8 by Ames strain of B. anthracis was 41 fold, while MCP-1 was 2 fold and IP-10 was 2.5 fold

(Figure 2). This result may indicate that IL-8 is a dominant chemokine in early response (4 hours exposure in our study) and neutrophils are the major player in early inflammatory response. Here we compared cytokines induced by B. anthracis and Yersinia exposures. Overall, Yersinia exposure induced higher levels of IL-1α, IL-1β, IL-6, IL-10 and TNFα than B. anthracis exposure, suggesting these cytokines could be used to develop an assay for discriminating Yersinia spp. from B. anthracis exposures. The vaccine strain (Sterne) of B. anthracis induced higher levels of IL-1β and TNFα than the virulent MEK inhibitor strain (Ames)

(Figure 2), suggesting these cytokines can contribute to a biomarker panel to discriminate if a particular isolate of B. anthracis is virulent. There was also a difference in induction of IL-10 between Y. pestis and near neighbors (Figure 2), suggesting this cytokine is a candidate biomarker for discriminating the virulence of Yersinia species. These data regarding Fenbendazole IL-10 expression following Yersinia spp. exposure are in agreement with published literature that shows Y. enterocolitica and Y. pestis can elicit statistically different levels of IL-10 expression [37]. Differences in IL-10 induction may be due to differences in the lcrV protein among Yersinia spp.[38]. The different cytokine profiles induced by B. anthracis and Yersinia here may be partially due to different surface antigens on the outermost part of these pathogens and the manner in which these bacteria were grown. Lipopolysaccharide (LPS), the main constituent of the outer membrane of Gram-negative bacteria, and peptidoglycan (PGN), the major cell wall component of Gram-positive bacteria, have been reported to elicit markedly different immune responses [39]. However, virulence factors, such as B. anthracis lethal toxin and Yersinia virulence antigen, LcrV, may also play important roles in differential cytokine induction. This view is supported by numerous reports that B.