Role of Macrophages in the Repair Process during the Tissue Migrating and Resident Helminth Infections

Figure 1

Immune response in tissue helminth infection. Lung tissue is usually affected during helminth migration; therefore, many repair mechanisms have been described for pulmonary tissue. The immune response is triggered when helminths disrupt the epithelial barrier. Helminths are a source of damage- and pathogen-associated molecular patterns (DAMPs and PAMPs), which activate various cells such as NK cells, epithelial cells, and innate lymphoid cells (ILCs). The production of IL-25 and IL-33 also activates ILCs, which are a main source of IL-5 that is important in eosinophil (Eos) activation. Eos bind antibodies linked to the parasite surface and release their intracytoplasmic enzymes during the acute phase of the infection, allowing parasite elimination; however, the surrounding tissue is also damaged. IL-25 and IL-33 also activate T helper lymphocytes type 2 (Th2), which in turn secretes IL-4 and IL-13, which promote B cell activation, antibody production, and the induction of alternative activated macrophages (AAMs). AAMs have two important mechanisms to decrease tissue damage. First, they inhibit the cytotoxic effect produced by classically activated macrophages (CAMs). Second, they produce enzymes, such as arginase-1 (Arg-1), that promote collagen production and deposition on damaged tissue, therefore restoring the function lost during CAMs and parasite-induced injury. AAMs also produce various cytokines (IL-10 and TGF-β) and chemokines (CCL-17, CCL-22, and CCL-24) and express markers such as YM-1, FIZZ-1, and MMR. On the other hand, CAMs are activated through IFN-γ production by natural killer (NK) cells and produce proinflammatory cytokines (IL-1β, IL-6, IL-12, IL-23, and TNF-α) and chemokines (CXCL-5, CXCL-9, and CXCL-10) and express iNOS that produces reactive oxygen species (ROS) and causes tissue damage. It is important to notice that although AAMs are fundamental in tissue repair, other cells such as ILCs and epithelial cells, which constitutively express Arg-1, may aid in tissue repair and produce collagen deposits in the damaged tissue.