TY - JOUR
T1 - Regulation of mammalian siderophore 2,5-DHBA in the innate immune response to infection
AU - Liu, Zhuoming
AU - Reba, Scott
AU - Chen, Wei Dong
AU - Porwal, Suheel Kumar
AU - Boom, W. Henry
AU - Petersen, Robert B.
AU - Rojas, Roxana
AU - Viswanathan, Rajesh
AU - Devireddy, L.
PY - 2014/6
Y1 - 2014/6
N2 - Competition for iron influences host-pathogen interactions. Pathogens secrete small ironbinding moieties, siderophores, to acquire host iron. In response, the host secretes siderophorebinding proteins, such as lipocalin 24p3, which limit siderophore-mediated iron import into bacteria. Mammals produce 2,5-dihydroxy benzoic acid, a compound that resembles a bacterial siderophore. Our data suggest that bacteria use both mammalian and bacterial siderophores. In support of this idea, supplementation with mammalian siderophore enhances bacterial growth in vitro. In addition, mice lacking the mammalian siderophore resist E. coli infection. Finally, we show that the host responds to infection by suppressing siderophore synthesis while up-regulating lipocalin 24p3 expression via TLR signaling. Thus, reciprocal regulation of 24p3 and mammalian siderophore is a protective mechanism limiting microbial access to iron.
AB - Competition for iron influences host-pathogen interactions. Pathogens secrete small ironbinding moieties, siderophores, to acquire host iron. In response, the host secretes siderophorebinding proteins, such as lipocalin 24p3, which limit siderophore-mediated iron import into bacteria. Mammals produce 2,5-dihydroxy benzoic acid, a compound that resembles a bacterial siderophore. Our data suggest that bacteria use both mammalian and bacterial siderophores. In support of this idea, supplementation with mammalian siderophore enhances bacterial growth in vitro. In addition, mice lacking the mammalian siderophore resist E. coli infection. Finally, we show that the host responds to infection by suppressing siderophore synthesis while up-regulating lipocalin 24p3 expression via TLR signaling. Thus, reciprocal regulation of 24p3 and mammalian siderophore is a protective mechanism limiting microbial access to iron.
UR - http://www.scopus.com/inward/record.url?scp=84901804753&partnerID=8YFLogxK
U2 - 10.1084/jem.20132629
DO - 10.1084/jem.20132629
M3 - Article
C2 - 24863067
AN - SCOPUS:84901804753
VL - 211
SP - 1197
EP - 1213
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 6
ER -