, 2002; Alemán et al., 2007). In the present study, early apoptosis was significantly decreased, whereas the late apoptosis

showed an increasing trend in H37Rv-infected neutrophils. Such accelerated apoptosis of neutrophils after interaction with mycobacteria is essential for the resolution of inflammation (Alemán et al., 2002; Hedlund et al., 2010). Apoptosis is also affected by the secretion of antiapoptotic or pro-apoptotic cytokines. TNF-α is one of selleck the best known pro-apoptotic cytokine. The increased secretion of TNF-α in H37Rv-infected neutrophils suggests its role in inducing late apoptosis and necrosis of these cells. On the other hand, the pro-inflammatory cytokine IFN-γ is antiapoptotic for neutrophils (Colotta et al., 1992) and gets secreted upon stimulation with appropriate agents (Ethuin et al., 2004). However, in this study, only basal expression of IFN-γ was observed under all infected conditions. This indicates that none of the strains were effective in the release of IFN-γ by neutrophils within a short span of 4 h culture. It is reported that TNF-α produced

by infected neutrophils is also involved in the activation of alveolar macrophages in noncontact cultures (Sawant & McMurray, PFT�� concentration 2007). To determine whether TNF-α produced by infected neutrophils modulates monocyte functions, the expression of CCR5 and CCR7 on monocytes was studied. Usually, the expression of CCR7 by peripheral monocytes is low or negative, and little upregulation happens after differentiation

into macrophages. Similarly, in this study, the expression of CCR7 Masitinib (AB1010) was low and not significant on monocytes stimulated with BCG- and Mw-infected NU sups. However, increased expression of CCR7 was observed with H37Rv-infected Nu sup. This might be due to increased secretion of TNF-α in H37Rv-infected Nu sup; however, this requires further experimental proof. On the other hand, CCR5 expression on peripheral monocytes is usually greater, and accordingly, its upregulation was observed under all infected conditions in this study. Although the exact mechanism for this upregulation is not known, it is sure to be neutrophil-mediated. In our previous report, we did not find any increase in the levels of MIP-1α (chemokine ligand of CCR5) at early time point of 3 h after infection of neutrophils with H37Rv (Pokkali et al., 2009). This basal level of chemokine may not be sufficient to bind to CCR5 and downregulate its expression level; instead, it may act as a trigger for the monocytes to upregulate CCR5 expression. In another study, when mononuclear cells were stimulated with MTB antigen, CCR5 expression on monocytes was increased, but CCR7 was hardly detectable (Arias et al., 2006). Interestingly, we observed increase in the expression of both the receptors on monocytes, supporting the fact that both CCR5- and CCR7-mediated monocyte signaling functions occur with the help of neutrophils.