Exploring the role of macrophages in determining the pathogenesis of liver fluke infection

Abstract

The food-borne trematodes, Opisthorchis viverrini and Clonorchis sinensis, are classified as group 1 biological carcinogens: definitive causes of cancer. By contrast, infections with Fasciola hepatica, also a food-borne trematode of the phylum Platyhelminthes, are not carcinogenic. This review explores the premise that the differential activation of macrophages during infection with these food-borne trematodes is a major determinant of the pathological outcome of infection. Like most helminths, the latter stages of infection with all 3 flukes induce M2 macrophages, a phenotype that mediates the functional repair of tissue damaged by the feeding and migratory activities of the parasites. However, there is a critical difference in how the development of pro-inflammatory M1 macrophages is regulated during infection with these parasites. While the activation of the M1 macrophage phenotype is largely suppressed during the early stages of infection with F. hepatica, M1 macrophages predominate in the bile ducts following infection with O. viverrini and C. sinensis. The anti-microbial factors released by M1 macrophages create an environment conducive to mutagenesis, and hence the initiation of tumour formation. Subsequently, the tissue remodelling processes induced by the M2 macrophages promote the proliferation of mutated cells, and the expansion of cancerous tissue. This review will also explore the interactions between macrophages and parasite-derived signals, and their contributions to the stark differences in the innate immune responses to infection with these parasites.

PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages

“…The M2 macrophages are capable of anti-inflammatory responses dominated by the secretion of IL-10 and TGF-β [ 26 ]. Many studies have revealed that helminth infection or helminth-derived products enable the induction of M2 macrophage polarization as a critical pathway or consequence of helminth infection-induced immunomodulation, with beneficial effects to both the parasite and host, including reduced inflammatory response and tissue damage [ 27 , 28 , 29 , 30 ]. The differential activation of macrophages during helminth infections determines the pathological outcome of the infection [ 27 ].…”

“…Many studies have revealed that helminth infection or helminth-derived products enable the induction of M2 macrophage polarization as a critical pathway or consequence of helminth infection-induced immunomodulation, with beneficial effects to both the parasite and host, including reduced inflammatory response and tissue damage [ 27 , 28 , 29 , 30 ]. The differential activation of macrophages during helminth infections determines the pathological outcome of the infection [ 27 ]. Late-stage (or chronic) infection with helminths usually induces M2 macrophages, along with functional repair of tissue damaged by the parasites [ 27 ].…”

Wound healing approach based on excretory-secretory product and lysate of liver flukes

“…It is necessary for fibroblast activation, which in turn stimulates keratinocyte proliferation and migration 37 . Parasitic nematodes are known to be able to activate M2 macrophage response in vivo and in vitro [38][39][40] . In our experiments, in specific treatment groups, a decrease in inflammatory infiltrated area of the wound was detected, as well as normal expression levels of Nos2 (M1-macrophages) and Arg1 (M2-macrophages) genes, comparable to unwounded healthy skin.…”

Foodborne trematodes: old foes, new kids on the block and research perspectives for control and understanding host–parasite interactions

“…In this regard, macrophages play an important role in the innate immune response against helminthiases in general, being classically or alternatively activated depending on the https://doi.org/10.1017/S0031182022000877 Published online by Cambridge University Press fluke life-stage (Lechner et al, 2021). In the next paper, Quinteros et al summarise the responses of macrophages to parasite-derived signals with a focus on liver flukes and discuss their importance in host susceptibility to fluke-induced cancer (Quinteros et al, 2022). These authors also highlight the need to view these cells not only as M1 or M2 types, but as multiple functional variants.…”

“…In the next paper, Quinteros et al . summarize the responses of macrophages to parasite-derived signals with a focus on liver flukes and discuss their importance in host susceptibility to fluke-induced cancer (Quinteros et al ., 2022). These authors also highlight the need to view these cells not only as M1 or M2 types, but as multiple functional variants.…”