**3. Tissue resident macrophages**

Macrophages, which are present in almost all body tissue and display distinct location-specific phenotypes and gene expression profiles, display remarkable functional diversity in innate immune responses, tissue development and tissue homeostasis [41]. In different organs, the resident macrophages are given various appellations: microglia cells have fundamental importance in assessing the pathogenetic significance of perivascular inflammatory phenomena within the brain [42]; Kupffer cells are resident and recruited macrophages that play major roles in the homeostatic function of the liver and in its response to tissue damage [43]; alveolar macrophages are key determinants pulmonary immune responses and in the lung inflammation caused by asthma [44]. Previously, it was hypothesised that tissue macrophages were recruited from circulating blood monocytes. Recent studies have demonstrated that tissue macrophages such as microglia, Kupffer cells and Langerhans cells are established prenatally and arise independently of the hematopoietic transcription factor Myb [45]. Myb is required for developing hematopoietic stem cells (HSCs) and all CD11bhigh monocytes and macrophages but is not required for yolk sac (YS) macrophages and for developing YS-derived F4/80bright macrophages. Such macrophages can persist independently of HSCs in several types of tissue in adult mice [46]. Kupffer cells as well as other resident macrophages (e.g., microglia) originate from the YS in a colony-stimulating factor-1/receptor (CSF-1R)-dependent and Myb-independent manner. Researchers have suggested that these macrophages are maintained by local proliferation, which results in extensive mitosis after stress or an exchanged tissue microenvironment [43, 47].

Macrophages are the most crucial and abundant immune cells. They can be categorised into two primary types according to function and differentiation: classically activated macrophages (M1 macrophages) and alternatively activated macrophages (M2 macrophages) [48]. Macrophages are relevant to innate resistance and to the relationship between inflammation and autoimmune disease. In mouse models, macrophages present CD11b, F4/80 and CSF-1R, with F4/80 being the surface proteins for M1 and M2 macrophages [49, 50]. When pathogens enter the organism from the intestinal portal vein, circulating monocytes (surrounding the pathogens and present in the peripheral blood) respond to chemokines (e.g., CCL2) and are exposed to antigens. While interacting with pattern recognition receptors (PRRs), antigens may exert either M1 or M2 polarising activities, depending on the Th1 (IFN-γ) and Th2 (IL-4 and IL-13) cytokines and immune factors [51, 52].
