Goblet cell metaplasia and mucin alterations in biliary epithelial cells during Opisthorchis viverrini infection in rodent models: Insights into host susceptibility and defense mechanisms

TL;DR

This study compares how two rodent species respond to a parasitic infection, finding that differences in mucus production affect whether the host resists or supports the parasite.

Contribution

The study reveals species-specific mucin dynamics and goblet cell metaplasia as key factors in susceptibility to Opisthorchis viverrini infection.

Findings

Mice produce acid mucins and show early hyperplasia, aiding worm clearance.

Hamsters produce sulfated mucins later, supporting parasite survival.

BrdU immunoreactivity correlates with worm clearance in mice but not in hamsters.

Abstract

Chronic Opisthorchis viverrini (OV) infection induces significant biliary changes and is a major risk factor for cholangiocarcinoma. However, the role of goblet cell metaplasia (GCM) and mucin dynamics in host defense and parasite persistence remains poorly understood. This study aims to characterize biliary histological changes, particularly mucin types, and compare responses between susceptible (hamsters) and non-susceptible (mice) hosts during early to chronic OV infection.

Thirty-five male golden Syrian hamsters and 35 male BALB/c mice were divided into infected and control groups. Infected animals received 50 OV metacercariae through gastric intubation and were sacrificed on days 1, 2, 7, 14, 28, and 56 post-infection. Histological, histochemical (Alcian Blue, periodic Acid-Schiff, and high iron diamine), and immunohistochemical (Bromodeoxyuridine [BrdU]) analyses were performed to assess mucin production, GCM, and bile duct proliferation.

Mice demonstrated an early, robust biliary response with pronounced hyperplasia and GCM characterized by acid mucin overproduction during the acute phase (days 1–28). Conversely, hamsters exhibited delayed biliary proliferation and GCM, with predominant sulfated mucins appearing during the chronic phase (days 28–56). BrdU immunoreactivity indicated earlier and stronger bile duct epithelial proliferation in mice, correlating with worm clearance by day 28. In hamsters, mucosal changes supported worm survival, as evidenced by continued parasite presence and egg production. Statistical analyses confirmed significant differences in mucin types and hyperplasia between species across infection stages.

Distinct mucosal responses in hamsters and mice reflect their susceptibility to OV infection. Acid mucins in mice facilitate worm expulsion, while sulfated mucins in hamsters appear to promote parasite persistence. These findings highlight the dual roles of mucins in host defense and parasite survival, providing insight into mechanisms underlying susceptibility and resistance in OV infections.

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