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

Abstract

The Th1/Th2/Th17 balance is a fundamental feature in the regulation of the inflammatory microenvironment during helminth infections, and an imbalance in this paradigm greatly contributes to inflammatory disorders. In some cases of helminthiasis, an initial Th1 response could occur during the early phases of infection (acute), followed by a Th2 response that prevails in chronic infections. During the late phase of infection, alternatively activated macrophages (AAMs) are important to counteract the inflammation caused by the Th1/Th17 response and larval migration, limiting damage and repairing the tissue affected. Macrophages are the archetype of phagocytic cells, with the primary role of pathogen destruction and antigen presentation. Nevertheless, other subtypes of macrophages have been described with important roles in tissue repair and immune regulation. These types of macrophages challenge the classical view of macrophages activated by an inflammatory response. The role of these subtypes of macrophages during helminthiasis is a controversial topic in immunoparasitology. Here, we analyze some of the studies regarding the role of AAMs in tissue repair during the tissue migration of helminths.

Effect of T. spiralis Serine protease inhibitors on TNBS-induced experimental colitis mediated by Macrophages

“…M2 phenotypic macrophages down-regulate Th1 type inflammatory response by releasing a large number of anti-inflammatory cytokines, and express resistin-like molecule alpha (RELM-α), Arg-1 and chitinase-3 (Ym1) on inflammatory tissue 29 . Consistent with the effect of helminth infection, the key immunomodulatory molecules of worms can also induce an increase in the activation of M2 phenotypic macrophages in the host 30 . Therefore, we speculate that TsKaSPI and TsAdSPI as members of the T. spiralis SPI superfamily may limit the occurrence and development of IBD by inducing the activation of M2 phenotype.…”

A Dual Role for Macrophages in Modulating Lung Tissue Damage/Repair during L2 Toxocara canis Infection

“…and 7 dpi (Figure 9b and d). Whereas TGF-β mRNA a factor associated with tissue repair produced by M2 macrophages [18] was modestly expressed in WT mice, its expression was significantly enhanced in STAT1 -/-mice at different dpi. Interestingly, STAT6 -/-mice failed to enhance TGF-β expression in lung tissue (Figure 9e and f).…”

“…Several studies with nematode-infected mice demonstrate the relevance of the balance between M1 and M2 macrophages and the molecules these cells release [18]. Notably, studies involving Heligmosomoides polygyrus [19] and Nippostrongylus brasiliensis [20], as well as the filarial nematodes Brugia malayi and Litomosoides sigmodontis [21], and the trematode Schistosoma japonicum [22] highlight an initial T-helper 1 (Th1)-M1 inflammation profile associated with tissue damage, followed by a Th2-M2 polarization that promotes tissue repair.…”

Helminths and intestinal barrier function

“…1,2 The mobilization of mucosal immunity in the context of enteric helminth infection is multi-faceted, complex and intriguing but a comprehensive discussion of such is beyond the scope of this commentary: the reader is referred to excellent recent reviews of this topic. [3][4][5][6][7][8] For the purposes of this review we will use 'epithelial permeability' to denote studies that address the physical properties of the epithelial layer and 'barrier function' is used as a more encompassing term that refers to the many extrinsic (e.g. mucus, IgA, commensal microbiota) components of the intestinal barrier.…”