What does this research mean for the field?

Thrombospondin-1 (TSP1) downmodulates lung inflammation and improves bacterial clearance during acute Pseudomonas aeruginosa infection by directly inducing IL-10 production in neutrophils via a PPARγ-dependent mechanism. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

This research aims to explore how thrombospondin-1 regulates lung inflammation through IL-10 production in neutrophils during Pseudomonas aeruginosa infection.

May 20, 2026

D101-18 Thrombospondin-1 Dowmodulates Lung Inflammation by Inducing Il-10 in Neutrophils During Acute Pseudomonas Aeruginosa Infection

Key Points

This research aims to explore how thrombospondin-1 regulates lung inflammation through IL-10 production in neutrophils during Pseudomonas aeruginosa infection.
In vivo models of Pseudomonas aeruginosa infection were used to study IL-10 regulation.
In vitro experiments demonstrated TSP-1's role in triggering IL-10 production in neutrophils.
Intratracheal transfer of IL-10 producing neutrophils in Thbs-1-/- mice was conducted one day prior to infection.
TSP-1 downmodulates pro-inflammatory activation of neutrophils and induces IL-10 production within 48 hours of infection.
Transfer of neutrophils producing IL-10 improved lung bacterial clearance and decreased pro-inflammatory cytokine production in Thbs-1-/- mice.
IL-10 was shown to regulate lung inflammation and host survival during acute Pseudomonas aeruginosa infections.

Abstract

Abstract Pseudomonas aeruginosa (PA) is a major cause of acute and chronic pulmonary infection globally and one of the 5 bacterial species that by 2019 caused 7% of the global mortality. The expression of multiple virulence factors PA causes a proteolytic pneumonia associated with elevated injury and high mortality due to antimicrobial resistance and limited therapeutic tools available.Thrombospondin-1 (TSP1) is a host glycoprotein that downregulates lung neutrophil pro-inflammatory activation during acute infection. In the current work, we demonstrate that TSP-1 does not only downmodulate the pro-inflammatory activation of neutrophils, but it also induces the production of IL-10 by these cells during the first 48 hours post infection in the lungs. Using in vivo models of infection, we determined that IL-10 regulates lung inflammation, host defense and survival. In addition, we demonstrate in vitro that TSP1 directly triggers IL-10 production in differentiated neutrophils in a mechanism dependent on the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ).Finally, we show that intratracheal transfer of neutrophils capable to produce IL-10 one day prior infection restores the production of lung IL-10 in Thbs-1-/- mice, improves lung bacterial clearance and reduces pro-inflammatory cytokine production.This data provides novel insight regarding the downstream regulation of the inflammatory response by TSP-1 that involves the production of IL-10 by neutrophils, immune cells that traditionally have been labeled as pro-inflammatory cells. In addition, it demonstrates the therapeutic potential of cell therapy to patients with reduced TSP1 and/or IL-10 expression that are infected with PA. This abstract is funded by: Agencia Nacional de Investigación y Desarrollo

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