Tuberculosis is an ancient infectious disease that remains a threat for public health around the world. Although the etiological agent as well as tuberculosis pathogenesis is well known, the molecular mechanisms underlying the host defense to the bacilli remain elusive. In this paper we focus on the innate immunity of this disease reviewing well-established and consensual mechanisms like Mycobacterium tuberculosis interference with phagosome maturation, less consensual mechanism like nitric oxide production, and new mechanisms, such as mycobacteria translocation to the cytosol, autophagy, and apoptosis/necrosis proposed mainly during the last decade. 1. Introduction The history of tuberculosis (TB) mixtures with the history of humanity since TB is one of the oldest infectious diseases affecting mankind. Bone TB was identified in 4000 years old skeletons, from Europe and Middle East, as the cause of death, showing that this disease was already a widespread health problem back then. In recorded history, Hippocrates writes about patients with wasting away associated with chest pain and coughing, frequently with blood in sputum. These symptoms allowed Hippocrates to diagnose TB, which at that time was called “consumption”. The frequency of descriptions of patients with these symptoms indicated that the disease was already well entrenched in ancient times. During the 16th and 17th centuries, the explosion of the European population and the growth of large urban centres made this continent the epicentre of many TB epidemics. Although during the first half of the 19th century, the incidence of TB peaked, causing death to approximately one quarter of the European population, in the second half of this century, TB mortality decreased due to improving sanitation and housing. The 20th century brought a steadily drop of morbidity and mortality due to TB, in the developed world, due to better public health practices, massive vaccination with Calmette-Guérin bacillus (BCG) vaccine and the advent of antibiotics such as streptomycin. This downward trend ended in the mid-1980s, triggered by emergence of acquired immunodeficiency syndrome (AIDS) and an increase in homelessness and poverty in the developed world. This fact pointed to the important role played by the immune system in this disease and also to the importance of socioeconomical factors. More recently, we assisted to the identification of multidrug resistant (MDR) strains, defined as mycobacteria resistance to at least rifampicin and isoniazid (two first line anti-TB drugs) and extensively drug resistant (XDR)
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