Triggering Receptor Expressed on Myeloid Cells (TREM)-2 Impairs Host Defense in Experimental Melioidosis

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. © 2016 weehuizen et al.