**1. Introduction**

There are millions of human pathogens grouped into about 1400 species [1]. The integumentary system serves as the first line of defence against infection; however, when the integumentary system fails, the immune system defends us against infectious pathogens [2, 3]. It consists of physical barriers such as the dermis, epidermis, and associated glands [4]. Innate immunity describes the initial reaction of the immune system to invasion by microbial pathogens by controlling tissue damage and coordinates the activation of the adaptive immune system [5–8]. When the integuments fail, innate immune cells like macrophages recognise pathogen-associated molecular patterns (PAMP) through pathogen recognition receptors (PRR) and are activated [9]. Macrophage responses involve phagocytosis of the PAMP and the release of inflammatory cytokines resulting in inflammation [10]. Inflammation is a natural reaction that can prevent tissue injury and heal wounded tissues. The strength of inflammation is proportionate to the severity of tissue injury [8, 11]. A normal inflammatory response is structured and involves; vasodilation, higher permeability of blood capillaries, blood clotting, an influx of many granulocytes and monocytes, and tissue swelling [8].

This review chapter will discuss various biomolecules and biochemical processes that regulate phagocytosis in macrophages.

## **2. The macrophage: functions and phenotypes**

Macrophages are crucial for mediating EFFECTS in the innate immune system [12]. Elie Metchnikoff first identified phagocytic cells in the 1900s and observed that macrophages effectively phagocytosed bacteria. Since then, there has been more research on macrophages—their types, function, polarisation, origin, and how they are regulated. Macrophage phagocytosis can be affected by its type, phenotype, and source. In addition, macrophages phagocytose other pathogens, such as viruses, fungi, and parasites [13]. They originate either from yolk-sac erythromyeloid progenitors or haematopoietic progenitors, thus generating monocyte-derived macrophages and tissue-resident macrophages. However, researchers have suggested heterogeneity in the origin of tissue-resident macrophages, as monocyte-derived macrophages can replace embryonic macrophages [8, 12, 14]. In addition, metabolic stimuli can regulate macrophage differentiation. For instance, haem and retinoic acid activate red pulp and peritoneal macrophage differentiation, respectively. Furthermore, tissue-resident macrophages contribute significantly to the heterogeneous functions of macrophages as they have specialised functions according to the tissue environment. Some examples of tissue-resident macrophages include alveolar macrophages, microglia, kupffer cells, and peritoneal macrophages [15].

#### **2.1 Function of macrophages**

The classical functions of macrophages include; cytokine secretion, the release of reactive oxygen species and reactive nitrogen species, removal of impaired cells and harmful micro-organisms, tissue surveillance, antigen presentation, T-cell activation, cytotoxicity and fibrosis [8, 16–18]. Tissue-resident macrophages carry out extra functions contingent upon the tissue requirements. For instance, alveolar macrophages clear away lung surfactants [19, 20]. Various stimuli coordinate macrophage fundamental functions and responses to tissue warning signals, including the presence of elements of microbial organisms [21].

In addition, macrophages participate in several pathologies that involve inflammation. For instance, macrophages regulate neuropathic and inflammatory pain by releasing cytokines and interacting with neurons [22]. In cancer, macrophages phagocytose tumour cells and participate in tumour immunosurveillance [23, 24]. In their research, Yang et al., 2021 [25] showed that macrophages could promote cartilage regeneration in mice where macrophage depletion hindered cartilage regeneration. Furthermore, macrophages encourage fibroblast proliferation. As a result, it regulates wound healing [26, 27]. Finally, poor differentiation of microglia during foetal development can cause neuropsychiatric disorders [28].

#### **2.2 Macrophage phenotypes**

There are three known macrophage phenotypes; M0 defines the macrophage in an inactive state, M1 defines a phenotype that promotes inflammation, and M2 defines a phenotype that resolves inflammation and promotes wound healing. In addition, M2 macrophages have four sub-phenotypes (M2a, M2b, M2c, M2d), which can affect the extent of phagocytosis [29, 30].

Lipopolysaccharide (LPS) and interferon-gamma (IFNγ), granulocyte-macrophage colony-stimulating factor (GMCSF), and PAMPs are conventional stimulators of the M1 macrophage phenotype. In contrast, macrophage colony-stimulating factors (MCSF), IL4, *Regulation of Phagocytosis in Macrophages DOI: http://dx.doi.org/10.5772/intechopen.109847*

IL10, and IL13 are stimulators of the M2 macrophage phenotype [8, 31, 32]. Macrophages show phenotypic characteristics based on an environmental stimulus. Epigenetic factors, including non-coding RNAs, histone modifications, and DNA methylation, can reprogram macrophages to switch between M1 and M2 phenotypes [24, 33–35]. Likewise, macrophage metabolic pathways participate in polarisation into different phenotypes. Lipid metabolism plays a significant role in macrophage phenotype formation. There are metabolic pathways specific to the M1 and M2 macrophage phenotype [36, 37].
