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Updated: Dec 21, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
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TREM2 suppresses the proinflammatory response to facilitate PRRSV infection via PI3K/NF-κB signaling

Zhenbang Zhu1, Xiaoxiao Zhang1, Wenjuan Dong1

  • 1State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR China.

Plos Pathogens
|May 14, 2020
PubMed

Insights

Triggering receptor expressed on myeloid cells 2 (TREM2) influences porcine reproductive and respiratory syndrome virus (PRRSV) replication. Targeting TREM2 offers a potential new strategy for controlling PRRSV infection in pigs.

Area of Science:

  • Immunology
  • Virology
  • Veterinary Medicine

Background:

  • Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to swine health.
  • Triggering receptor expressed on myeloid cells 2 (TREM2) is an anti-inflammatory receptor expressed on macrophages, key targets of PRRSV.

Purpose of the Study:

  • To investigate the role of TREM2 in PRRSV infection within porcine alveolar macrophages (PAMs).
  • To elucidate the mechanisms by which TREM2 influences PRRSV replication and the host immune response.

Main Methods:

  • In vitro studies using PAMs to assess TREM2 expression and function during PRRSV infection.
  • TREM2 silencing and overexpression experiments to determine its effect on viral replication.
  • Analysis of signaling pathways (PI3K/NF-κB) and cytokine production.
  • In vivo studies in pigs challenged with PRRSV to evaluate TREM2 expression in tissues and soluble TREM2 (sTREM2) levels.

Main Results:

  • PRRSV infection increased TREM2 expression in PAMs.
  • TREM2 silencing reduced PRRSV replication, while overexpression enhanced it.
  • TREM2 interacted with PRRSV Nsp2.
  • TREM2 downregulation activated PI3K/NF-κB signaling, increasing proinflammatory cytokines and type I interferons.
  • Activated metalloproteinase 17 (ADAM17) cleaved CD163, suppressing infection.
  • Exogenous sTREM2 inhibited PRRSV attachment.
  • In vivo, PRRSV challenge increased TREM2 expression and sTREM2 production in pigs.

Conclusions:

  • TREM2 plays a critical role in regulating PRRSV replication through modulation of the inflammatory response.
  • TREM2 interacts with PRRSV Nsp2 to facilitate infection.
  • Targeting TREM2 presents a novel therapeutic approach for controlling PRRSV infections in swine.

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