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Updated: Mar 20, 2026
Simplified Whole Body Plethysmography to Characterize Lung Function During Respiratory Melioidosis
Published on: February 24, 2023
Triggering Receptor Expressed on Myeloid Cells (TREM)-2 Impairs Host Defense in Experimental Melioidosis
Tassili A F Weehuizen1,2, Tijmen J Hommes1,2, Jacqueline M Lankelma1,2
1Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Netherlands.
Background:
Triggering receptor expressed on myeloid cells (TREM) -1 and TREM-2 are key regulators of the inflammatory response that are involved in the clearance of invading pathogens. Melioidosis, caused by the "Tier 1" biothreat agent Burkholderia pseudomallei, is a common form of community-acquired sepsis in Southeast-Asia. TREM-1 has been suggested as a biomarker for sepsis and melioidosis. We aimed to characterize the expression and function of TREM-1 and TREM-2 in melioidosis.
Methodology/Principal Findings:
Wild-type, TREM-1/3 (Trem-1/3-/-) and TREM-2 (Trem-2-/-) deficient mice were intranasally infected with live B. pseudomallei and killed after 24, and/or 72 h for the harvesting of lungs, liver, spleen, and blood. Additionally, survival studies were performed. Cellular functions were further analyzed by stimulation and/or infection of isolated cells. TREM-1 and TREM-2 expression was increased both in the lung and liver of B. pseudomallei-infected mice. Strikingly, Trem-2-/-, but not Trem-1/3-/-, mice displayed a markedly improved host defense as reflected by a strong survival advantage together with decreased bacterial loads, less inflammation and reduced organ injury. Cellular responsiveness of TREM-2, but not TREM-1, deficient blood and bone-marrow derived macrophages (BMDM) was diminished upon exposure to B. pseudomallei. Phagocytosis and intracellular killing of B. pseudomallei by BMDM and alveolar macrophages were TREM-1 and TREM-2-independent.
Conclusions/Significance:
We found that TREM-2, and to a lesser extent TREM-1, plays a remarkable detrimental role in the host defense against a clinically relevant Gram-negative pathogen in mice: TREM-2 deficiency restricts the inflammatory response, thereby decreasing organ damage and mortality.
Insights
Triggering receptor expressed on myeloid cells (TREM)-2 deficiency improves host defense against Burkholderia pseudomallei. This study shows TREM-2, not TREM-1, detrimentally impacts melioidosis outcomes in mice.
Area of Science:
- Immunology
- Microbiology
- Pathogen Defense
Background:
- Triggering receptor expressed on myeloid cells (TREM)-1 and TREM-2 regulate inflammatory responses and pathogen clearance.
- Melioidosis, caused by Burkholderia pseudomallei, is a significant cause of sepsis in Southeast Asia.
- TREM-1 is a potential biomarker for sepsis and melioidosis.
Purpose of the Study:
- To investigate the expression and function of TREM-1 and TREM-2 in experimental melioidosis.
- To determine the role of TREM-1 and TREM-2 in host defense against Burkholderia pseudomallei.
Main Methods:
- Intranasal infection of wild-type, TREM-1/3 deficient, and TREM-2 deficient mice with B. pseudomallei.
- Analysis of survival, bacterial load, inflammation, and organ injury.
- Assessment of cellular responsiveness, phagocytosis, and intracellular killing by isolated macrophages.
Main Results:
- TREM-1 and TREM-2 expression increased in the lungs and livers of infected mice.
- TREM-2 deficient mice showed significantly improved survival, reduced bacterial loads, less inflammation, and decreased organ injury compared to wild-type mice.
- Cellular responsiveness of TREM-2 deficient macrophages was diminished, but phagocytosis and intracellular killing were TREM-1 and TREM-2 independent.
Conclusions:
- TREM-2 plays a detrimental role in host defense against B. pseudomallei.
- TREM-2 deficiency restricts inflammation, leading to reduced organ damage and mortality in melioidosis.
- TREM-1 has a lesser, though still detrimental, role in this infection model.
