The role of neutrophils, the predominant cells harboring replicating Mtb during TB, is being actively explored and its accumulation is associated with lung pathology. Using the well-established mouse model of TB, the role of constitutively expressed neutrophilic protein, S100A8/A9 mediated neutrophil accumulation during progression to chronic TB was established (Gopal et al. 2013). The abrogation of neutrophils or S100A8/A9 improves Mtb control during chronic phase of the disease. Extensive collaborative work conducted in the NHP model of TB with the Kaushal Lab, Texas Biomedical Research Institute, and in human studies has substantiated our findings in the mouse model. The focus of our ongoing studies is to exploit the signaling pathways that control S100A8/A9 expression and target it to decrease Mtb disease susceptibility to enable host directed therapy for TB. Additionally, S100A8/A9 in conjunction with other chemokine markers in blood serum / urine are being explored as candidate targets to develop a rapid diagnostic test for TB.