**2. The innate immune response against tuberculosis and the host-pathogen interaction with mycobacteria**

The main entrance gate of MTB to the human body is the lung. There, air particles can be cleared by sneezing and coughing. Also, the presence of cilia and mucus contributes to the removal of particles allocated in deeper locations. In addition to that, the epithelia at the lung provide biochemical mechanisms to battle pathogens; among them the hydrolytic enzyme Lysozyme, and peptides (such as cathelicidins and defensins) contribute to the innate immune response through pathogen membrane destruction [13]. Microorganisms that cannot be cleared by these means will be phagocyted by alveolar macrophages (AM). During MTB infection, macrophages become a cellular niche of survival and bacterial multiplication. However, AM are not the only innate immune cells that interplay with MTB, neutrophils, dendritic cells, NK cells (natural killer) also interact with the pathogen.

*Phagocytosis of* Mycobacterium tuberculosis*: A Narrative of the Uptaking and Survival DOI: http://dx.doi.org/10.5772/intechopen.110067*

Mycobacterial recognition by macrophages begins with the cell expression of a variety of phagocytic pattern recognition receptors (PPRs) that identify MTB through PAMPs. Cellular receptors of the C-type lectin receptors (CLRs) recognize microorganisms through carbohydrate patterns; among these receptors are mannose receptor (MR), Mincle, dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN), and Dectin-1. Also, complement receptors (CR) and immunoglobulin receptors assist in the recognition of opsonized mycobacteria. Likewise, receptors that contribute to mycobacterial interaction are Toll-like receptors (TLRs), Scavenger receptors (SRs), NOD-like receptors (NLRs), and CD14 [14, 15]. These PPRs (which intervened and were stimulated during the interaction with MTB) determine the outcome of the acquired immune response, survival, autophagy, and apoptosis [16].

#### **2.1 Dendritic cells**

Dendritic cells originate from bone marrow progenitor cells and migrate as immature cells to different anatomical locations in order to detect pathogens. Part of their function as presenting cells is being an important link between the innate and acquired immune response. After recognition and phagocytosis of antigens (Ag) or pathogens, they increase the expression of MHC I and II [17]. Then, dendritic cells migrate through lymphatic circulation to lymph nodes after antigen processing [18]. At this location, dendritic cells induce T-cell activation through antigen presentation to lymphocytes [19]; however, MTB limits the response of dendritic cells as part of the immune response evasion [20], and moreover, the increased number of MTB found inside the dendritic cells suggests the replication of it (event associated with an increased expression of IL-10) [21]. Additionally, dendritic cells infected with MTB induce the expression of cytokines such as IFN alpha and beta, which contribute to the cell migration of NK cells and T cells, and might promote granuloma formation [22].

#### **2.2 Neutrophils**

If neutrophils are present in the lungs before infection, they reduce the bacterial number; however, if they are absent immediately after infection, the bacterial count increases [23, 24]. During MTB infection, neutrophils are recruited to the site of infection due to the cytokine and chemokine expression [25]. Neutrophils exert the innate immune response against MTB through diverse mechanisms, such as bacterial phagocytosis, production of hypochlorous acid, expression of enzymes that destroy bacteria and human cells indiscriminately, and the release of the neutrophil extracellular traps (NETs) [26].

#### **2.3 NK cells**

NK cells are lymphocytes that contribute directly to the innate immunity. As part of their capabilities, they produce cytokines to assist the acquired and innate immune response. NK cells destroy infected cells through chemical weapons such as perforin, granzyme, defensin, and NO (nitric oxide). It has been observed that during MTB infection in T cells-deficient mice, NK cells contribute to the resistance against the bacteria. In that regard, in T cell-deficient individuals, the expression of IFN gamma enhances the mycobacterial control [27].

#### **2.4 Macrophages**

Macrophages are hematopoietic-derived cells from bone marrow, which are distributed almost throughout the human body. They eliminate foreign particles and microorganisms, remove cell debris, and contribute to homeostasis. When MTB is present in the lungs, alveolar macrophages constitute the central place of survival, growth, and control of it. Furthermore, macrophages comprise the tie with the acquired immune response (which is the responsibility of the outcome of the pathology).

During infection, AM regulate precisely the inflammatory and anti-inflammatory response in order to reduce tissue damage [28].

The mycobacterial recognition through PAMPs, identified by PPRs in the macrophage, induces immune response and phagocytosis. MTB recognition is mediated by TLR, NLRs, and CTLs [29, 30]. On the other hand, phagocytosis is dependent on the interaction of bacteria with macrophage receptors such as MR and DC-SIGN [31]. Additionally, the macrophage activation has been related to the intervention of the NOD2, MR, Mincle, DC-SIGN, Dectin, and TLR 2, 4, and 9 receptors [32].

Mycobacteria phagocytosis is dependent on the movement of cytoskeleton proteins; after the bacteria is located in the phagosome, ATPases are engaged in order to acidify it. Then, the phagosome merges with the lysosome and the content is poured. However, these microbicidal mechanisms (and some others that will be discussed later) are manipulated by MTB in order to survive and replicate inside the macrophage.
