Acidification of macrophage phagosomes serves an important bactericidal 
function. We show here that the redox-sensitive transient receptor potential 
(TRP) cation channel TRPM2 is expressed in the phagosomal membrane and regulates 
macrophage bactericidal activity through the activation of phagosomal 
acidification. Measurement of the TRPM2 current in phagosomes identified TRPM2 
as a functional redox-sensitive cation channel localized in the phagosomal 
membrane. Simultaneous measurements of phagosomal Ca2+ changes and phagosome 
acidification in macrophages undergoing phagocytosis demonstrated that TRPM2 was 
required to mediate the efflux of cations and for phagosomal acidification 
during the process of phagosome maturation. Acidification in phagosomes was 
significantly reduced in macrophages isolated from Trpm2-/- mice as compared to 
wild type, and acidification was coupled to reduced bacterial clearance in 
Trpm2-/- mice. Trpm2+/+ macrophages treated with the vacuolar H+-ATPase 
inhibitor bafilomycin showed reduced bacterial clearance, similar to that in 
Trpm2-/- macrophages. Direct activation of TRPM2 using adenosine diphosphate 
ribose (ADPR) induced both phagosomal acidification and bacterial killing. These 
data collectively demonstrate that TRPM2 regulates phagosomal acidification, and 
is essential for the bacterial killing function of macrophages.