**3. IL-1β signalling pathway in tuberculosis**

IL-1β imparts immunity to tuberculosis and mice lacking in IL-1β or its receptors are suscep‐ tible to M tb infection (Mayer-Barber KD, 2010). It is an important factor in host immunity and virulent mycobacteria suppress the IL-1β production which is regulated by type I interferons in macrophages (Novikov A et al., 2011). IL-1β has been shown to possess bactericidal activity in the macrophages derived from murine and humans (Jayaraman P et al., 2013). It upregulates secretion of tumor necrosis factor (TNF) and cell surface expression of TNFR1, thus facilitates TNF signalling which culminates in caspase-3 activation leading to growth inhibition of M tb through apoptosis of the infected macrophage (Jayaraman P et al., 2013). They also showed that this effect of TNF on the M tb infected macrophage is due to autocrine mode of action. In synergy with vitamin D, IL-1β drives transcriptional expression of the antimicrobial peptide genes such as defensin beta 4 (DEFB4), cathepsins, cathelicidins and ubiquitin derived peptides which have M tb killing ability (Alonso S, 2007; Liu PT et al, 2009; Ottenhoff TH, 2012). Results from the work of Liu PT et al. 2009, also suggest that the coherent action of IL-1β and vitamin D is an integral part of the TLR2/1 signalling mediated antimicrobial activity.

IL-1β being a pro-inflammatory cytokine is under tight regulation to prevent the immunepathology and subsequent tissue damage during chronic infections. Mishra et al., 2013, showed that level of this cytokine is regulated by IFN-γ induced release of nitric oxide (NO) which in turn regulate the inflammasome NLRP3 (nucleotide binding and oligomerization domain-like receptor family pyrin domain containing 3) during M tb infections. This regulation happens at the stage of caspase1 mediated processing of pro-IL-1β to IL-1β and is specifically NLRP3 dependent (Mishra BB. et al., 2013).
