**1. Introduction**

*Mycobacterium tuberculosis* (MTB) is a human pathogen, which belongs to a group of nine species phylogenetically related, called *M. tuberculosis* complex [1]. MTB is the causative agent of tuberculosis: An infectious disease that causes mainly a pulmonary infection although, renal, meningeal, genital tuberculosis, and other anatomical sites have been affected. Is a human pathogen and both (human hosts and MTB) have coevolved together for an extended period of time of approximately 70,000 years [2].

Before the COVID-19 pandemic, tuberculosis (TB) was the first cause of death from a single infectious agent. It is estimated that 25% of the global population is infected with the bacteria*,* but only 10% of them will develop the disease during their lifetime. TB continues to be a public health problem due to the increased number of co-infections in HIV patients and the augmented antimicrobial resistance by MTB [3].

The mycobacterial infection in humans originates by the inhalation of aerosols containing the bacteria on *flügge* droplets, which is dispersed by the sneeze or cough of infected individuals. Once in the alveolus, the microorganism interacts with the

innate immune response cells; the receptors at the macrophage identify the bacteria through pathogen-associated molecular patterns called PAMPs, and the said PAMPs are composed of lipids, carbohydrates, and protein characteristic of the mycobacteria and other pathogens [4]. During this initial immune response against tuberculosis, various cell types interact with the bacteria, such as dendritic cells, NK cells, neutrophils, and macrophages [5–7].

The phagocyted MTB can survive inside the macrophages through specific strategies. Namely, evasion of the immune response by phagosome, arresting inhibition of phagosome acidification [8], resistance to nitrogen species and reactive oxygen species [9], and also apoptosis and autophagy evasion [10]. The previously mentioned survival mechanisms are live-defining determinants on which mycobacterial efficiency to invade, establish, and survive inside macrophages depends. The phagocytosis constitutes a fundamental event during host-pathogen interaction in TB because this initial interplay determines the outcome of the disease.

As described before, MTB evades the immune response inside the macrophages, it uses the cell as a niche to survive latently, and it even multiplies efficiently within the phagocytic cell during reduced immune containment. The host search for containment and isolation produces cytokines and chemokines, which induce the migration of cells, and thus, granuloma formation. At the beginning of granuloma formation, the immune cells that constitute the granuloma are monocytes, neutrophils, and macrophages; subsequently after, the development of the acquired immune response induces the migration of lymphocytes. At times, the presence of extracellular matrix components and fibroblasts has been found around the mycobacterial granuloma [11, 12].

In the next sections, the initial process of human tuberculosis infection by MTB will be reviewed, focusing on:

