Trichinella spiralis HSP70 Mediates Mice Immune Responses via TLR2/MyD88/ERK Signaling Pathway

Trichinellosis is a globally important zoonotic parasitic disease that poses a significant threat to public health and causes substantial economic losses. Trichinella spiralis heat shock protein 70 (Ts‐HSP70) has been identified as a potential vaccine candidate with immunomodulatory properties. However, the underlying mechanisms by which Ts‐HSP70 regulates host immune responses remain incompletely understood. In this study, we investigated the role of Ts‐HSP70 in modulating macrophage functions and explored its involvement in Toll‐like receptor 2 (TLR2)‐mediated signaling. The interaction between Ts‐HSP70 and mouse TLR2 was examined using co‐immunoprecipitation (Co‐IP) and fluorescence colocalization assays. Recombinant Ts‐HSP70 (rTs‐HSP70) was used to stimulate RAW264.7 macrophages in vitro, and its effects on cell proliferation, phagocytosis, nitric oxide (NO) production, reactive oxygen species (ROS) generation, and cytokine mRNA expression were evaluated. rTs‐HSP70 significantly enhanced macrophage proliferation and phagocytic activity, increased NO and ROS production, and upregulated the mRNA expression of IL‐1β, IL‐6, TNF‐α, and IL‐10. In addition, rTs‐HSP70‐induced activation of NF‐κB and MAPK signaling pathways. Functional inhibition assays further suggested that ERK activation was partially dependent on the TLR2/MyD88 pathway. Furthermore, rTs‐HSP70 encapsulated in poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles elicited specific antibody responses and conferred partial protection in mice, as evidenced by a 28.0% reduction in muscle larval burden. Collectively, these findings indicate that Ts‐HSP70 modulates macrophage immune functions and may contribute to host defense through TLR2‐associated signaling, providing insights into its potential application in vaccine development against trichinellosis.