Innate immunity in tuberculosis: myths and truth

Tuberculosis is the most important bacterial infection world wide. The causative agent, Mycobacterium tuberculosis survives and proliferates within macrophages. Immune mediators such as interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) activate macrophages and promote bacterial killing. IFN-gamma is predominantly secreted by innate cells (mainly natural killer (NK) cells) and by T cells upon instruction by interleukin 12 (IL-12) and IL-18. These cytokines are primarily produced by dendritic cells and macrophages in response to Toll-like receptor (TLR) signalling interaction with tubercle bacilli. These signals also induce pro-inflammatory cytokines (including IL-1beta and TNF-alpha), chemokines and defensins. The inflammatory environment further recruits innate effector cells such as macrophages, polymorphonuclear neutrophils (PMN) and NK cells to the infectious foci. This eventually leads to the downstream establishment of acquired T cell immunity which appears to be protective in more than 90% of infected individuals. Robust innate immune activation is considered an essential prerequisite for protective immunity and vaccine efficacy. However, data published so far provide a muddled view of the functional importance of innate immunity in tuberculosis. Here we critically discuss certain aspects of innate immunity, namely PMN, TLRs and NK cells, as characterised in tuberculosis to date, and their contribution to protection and pathology.