Protective Immunity to Mycobacterium tuberculosis Infection by Chemokine and Cytokine Conditioned CFP-10 Differentiated Dendritic Cells

BACKGROUND: Dendritic cells (DCs) play major roles in mediating immune responses to mycobacteria. A crucial aspect of this is the priming of T cells via chemokines and cytokines. In this study we investigated the roles of chemokines RANTES and IP-10 in regulating protective responses from Mycobacterium tuberculosis (M. tb) 10 kDa Culture Filtrate Protein-10 (CFP-10) differentiated DCs (CFP10-DCs). METHODS AND FINDINGS: Infection of CFP10-DCs with mycobacteria down-modulated RANTES and IP-10 levels. Pathway specific microarray analyses showed that in addition to RANTES and IP-10, mycobacteria infected CFP10-DCs showed reduced expression of many Th1 promoting chemokines and chemokine receptors. Importantly, T cells co-cultured with RANTES and IP-10 conditioned CFP10-DCs mediated killing of mycobacteria from infected macrophages. Similarly, T cells recruited by RANTES and IP-10 conditioned CFP10-DCs mediated significant killing of mycobacteria from infected macrophages. IFN-gamma treatment of CFP10-DCs restored RANTES and IP-10 levels and T cells activated by these DCs mediated significant killing of virulent M. tb inside macrophages. Adoptive transfer of either RANTES and IP-10 or IL-12 and IFN-gamma conditioned CFP10-DCs cleared an established M. tb infection in mice. The extent of clearance was similar to that obtained with drug treatment. CONCLUSIONS: These results indicate that chemokine and cytokine secretion by DCs differentiated by M. tb antigens such as CFP-10 play major roles in regulating protective immune responses at sites of infection

How ‘bad apples’ spoil the bunch: Faultlines, emotional levers and exclusion in the workplace

Just as a rotten apple makes other apples around it begin to decay, so too can people influence others within their vicinity, particularly in terms of destructive emotions and behaviors. Trevino and Youngblood (1990) adopted the term ‘bad apples’ to describe individuals who engage in unethical behaviors and who also influence others to behave in a similar manner. In this chapter, the ‘bad apple’ metaphor is adopted to describe the employee whose actions and interactions create and maintain destructive faultlines and unethical exclusion behaviors that negatively impact the emotional well-being and effective and ethical performance of the team. In particular, the chapter examines the way in which ‘bad apples’ use destructive emotion management skills through the manipulation of emotional levers of others, what motivates them to do so and the implications it may have on management