Ts-Hsp70 confers dual-stage protective immunity against Trichinella spiralis infection by sustaining M1 macrophage polarization in mice
Year: 2026
Type: article
Abstract: Background Trichinellosis is a globally significant zoonotic parasitic disease for which effective preventive strategies remain elusive. Our previous studies identified Ts -Hsp70 as a promising vaccine candidate antigen against Trichinella spiralis , although its precise mechanism of immune protection is not fully understood. Macrophages (Mφ) play pivotal roles in anti-helminth immunity and undergo dynamic M1/M2 polarization shifts during different stages of T. spiralis infection. Objective To investigate whether Ts -Hsp70 enhances host resistance against T. spiralis infection by reprogramming macrophage polarization to provide multi-stage protection. Methods The role of macrophages in worm expulsion was confirmed via macrophage depletion using clodronate liposomes (CloA). In vivo , cytokine levels (ELISA) and macrophage polarization (flow cytometry, immunofluorescence) were assessed in the spleen, mesenteric lymph nodes (MLN), intestine, and muscle of Ts -Hsp70-immunized mice at 1, 5, 15, and 30 days post-infection (dpi). In vitro studies evaluated the direct effects of Ts -Hsp70 on macrophage phenotype, phagocytic capacity, and T-cell activation. Results Macrophage depletion significantly abrogated Ts -Hsp70-mediated expulsion of both adult worms (early stage) and muscle larvae (mid-late stage). In vivo , Ts -Hsp70 immunization promoted a sustained M1-dominated response, increased pro-inflammatory cytokines (IFN-γ, TNF-α) and reduced anti-inflammatory cytokines (IL-4, IL-10) in serum. This shift significantly increased M1/M2 ratios across peripheral organs (spleen, MLN) and local infection sites (intestine, muscle) during mid-late infection. In vitro , Ts -Hsp70 directly induced M1 markers (iNOS, CD80, TNF-α), enhanced phagocytic activity, and promoted CD4 + T-cell proliferation. Conclusion Ts -Hsp70 confers dual-stage protection against T. spiralis by sustaining M1 macrophage polarization—promoting early adult worm expulsion and disrupting larval survival in later stages. These findings elucidate the mechanism underlying Ts -Hsp70-induced immune protection and reinforce its potential as an effective vaccine antigen against trichinellosis.
Source: Frontiers in Immunology
Institution: Capital Medical University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7154067337