Protection Vs. Pathology in Tuberculosis: How Our Growing Understanding of the Molecular Regulators of Cell Recruitment Could Lead to New Therapies

Abstract

The granuloma is the hallmark pathological structure in patients infected with Mycobacterium tuberculosis (Mtb). It is a collection of mostly innate and adaptive immune cells organized around Mtb bacilli with a defined spatial arrangement and cellular composition [1-3]. Infection with Mtb begins after a few inhaled bacilli are phagocytosed by lung-resident macrophages. Infected macrophages release of TNFα, which initiates a cytokine storm and supports the release of other pro-inflammatory cytokines and chemokines like Il-1β, IL-6, Il-12, CCL2, and, CCL5, to name a few [4]. Eventually, dendritic cells from the granuloma transport bacterial antigen to the lymph node and activate Mtb-specific CD4 and CD8 T-cells, which then migrate to the granuloma and enhance macrophage anti-microbial activity with the release of IFNγ [5-8].