**4. Immunomodulation of macrophages in the immune system**

Polysaccharides extracted from mushrooms or algae have immunomodulatory functions, such as increasing macrophage activity, regardless of whether innate or adaptive immunity is activated [64]. For instance, the phagocytic activity of cells, the killing ability of natural killer cells, and the promotion of immune cells to secrete cytokines activate the immune system. In our previous laboratory studies, mushroom polysaccharide administration could enhance the tumour-suppressive and antiallergic ability in mice, along with significant enhancement in the woundhealing ability in rats. Immune cells of the innate immune response, such as macrophages and dendritic cells, or other nonimmune cells, such as epithelial cells, have many nonspecific recognition receptors associated with antigens that evade pathogens. Based on molecular identification and binding, complement receptor type 3 (CR3) on these cells can identify polysaccharides [65]. When polysaccharides bind to CR3, it triggers a series of signalling to activate transcription factors. Cells secrete a cytokine that triggers an inflammatory response, and the antigen exhibits the major histocompatibility complex of the cell, thereby activating other immune cells to achieve immunomodulatory functions [66, 67]. Dectin-1 belongs to the c-type lectin receptor family and is expressed on the cell membranes of macrophages, dendritic cells, neutrophils, and T and B cells [68]. Dectin-1 binds to polysaccharides to promote macrophage phagocytosis and respiratory burst; it also promotes the degranulation of neutrophils and secretion of cytokines and chemokines from immune cells [69–72]. Polysaccharides from *Antrodia camphorata* were cocultured with immature dendritic and T cells isolated from healthy human blood, and the polysaccharides could promote dendritic cell maturation and stimulate T-cell proliferation and IFN-γ performance [73, 74]. Coculture of polysaccharides with macrophages can promote the secretion of immune-related factors and cytokine gene expression, such as nitric oxide (NO), tumour necrosis factor (TNF)-α, IL-1β, and IL-6, to promote macrophage activity [75–78].

Based on our teams' experimental results, the functional polysaccharide can stimulate macrophages and further activate cytokines TNF-α, IL-12, IFN-γ, IL-2, IL-4, IL-10, and IL-17, which are associated with apoptosis and cell cycle. Growth hormone, a multipeptide hormone regulator, promotes growth and cell proliferation [75, 78, 79]. Polysaccharides can reduce CCl4-induced liver damage by regulating related antioxidant enzymes and effectively reducing oxidative damage in liver tissue [80, 81]. In mice, intraperitoneal polysaccharide injection could effectively prevent lipid peroxidation and inhibit the production of reactive oxygen species in the liver [82, 83]. Taken together, the immunomodulation function of polysaccharides may effectively regulate cellular immune response [84].

### **5. Immunomodulation of macrophage differentiation**

Immune cells are crucial in immune response modulation. As mentioned, macrophages polarise into M1 and M2 macrophages, which have distinct functions and are affected by the physiological microenvironment factors. M1 macrophages perform pathogen elimination through phagocytosis, inflict oxidative damage, and complement system activation. M2 macrophages have tissue recovery functions. Tumour tissues contain considerable amounts of M2 macrophages that release angiogenesis-promoting growth factors.

Inflammatory reactions can induce chronic diseases; thus, reducing inflammation is important for inhibiting chronic disease. To achieve anti-inflammatory effects, immunotherapy is a novel therapeutic approach without known side effects

**99**

*Mucosal Macrophage Polarization Role in the Immune Modulation*

and drug resistance problems. However, anti-inflammatory processes involve complex reactions; for instance, cellular ROS production for eliminating pathogens can also induce cellular apoptosis [85, 86]. Thus, the balance between inflammatory and anti-inflammatory processes is essential. In case of any imbalance, natural functional materials, such as triterpenoids and polysaccharides, can be applied for

In summary, polysaccharides can regulate macrophage differentiation to modulate host physiological response through cytokine secretion. Polysaccharides, such as beta-glucan, are known biological response modifiers that can activate leukocytes, monocytes, and macrophages [87, 88]. The activation mechanism involves the polysaccharides binding to the receptors, such as Toll-like receptor, expressed on AMs or Kupffer, Langerhans, mesangial, or microglial cells. After the binding, the immune cells are activated via Toll-like receptor four-mediated signalling pathways to modulate the immune capacity. The activated immune cells then produce IFN-γ, TNF-α, ILs, and other cytokines to modulate the anti-inflammatory process. In conclusion, the use of the functional materials as alternative medicines in clinical therapy is feasible; however, before implementation, the substance's immunomodulatory mechanism should be clearly realised, particularly in the immune

This project was supported by the Ministry of Science and Technology, Taiwan

None of the authors has a financial relationship with a commercial entity that

and Yu-Sheng Wu1

1 Department of Aquaculture, National Pingtung University of Science and

2 Department of Life Science, National Taiwan University, Taipei, Taiwan

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: wuys0313@mail.npust.edu.tw

\*

*DOI: http://dx.doi.org/10.5772/intechopen.86609*

immunomodulation.

cell signal transduction.

**Acknowledgements**

**Conflict of interest**

**Author details**

Tsung-Meng Wu1

Technology, Pingtung, Taiwan

provided the original work is properly cited.

(MOST. 107-2313-B-020-004).

has an interest in the subject of this manuscript.

, Shiu-Nan Chen<sup>2</sup>

*Mucosal Macrophage Polarization Role in the Immune Modulation DOI: http://dx.doi.org/10.5772/intechopen.86609*

and drug resistance problems. However, anti-inflammatory processes involve complex reactions; for instance, cellular ROS production for eliminating pathogens can also induce cellular apoptosis [85, 86]. Thus, the balance between inflammatory and anti-inflammatory processes is essential. In case of any imbalance, natural functional materials, such as triterpenoids and polysaccharides, can be applied for immunomodulation.

In summary, polysaccharides can regulate macrophage differentiation to modulate host physiological response through cytokine secretion. Polysaccharides, such as beta-glucan, are known biological response modifiers that can activate leukocytes, monocytes, and macrophages [87, 88]. The activation mechanism involves the polysaccharides binding to the receptors, such as Toll-like receptor, expressed on AMs or Kupffer, Langerhans, mesangial, or microglial cells. After the binding, the immune cells are activated via Toll-like receptor four-mediated signalling pathways to modulate the immune capacity. The activated immune cells then produce IFN-γ, TNF-α, ILs, and other cytokines to modulate the anti-inflammatory process.

In conclusion, the use of the functional materials as alternative medicines in clinical therapy is feasible; however, before implementation, the substance's immunomodulatory mechanism should be clearly realised, particularly in the immune cell signal transduction.
