Inoculation with viable, but not inactivated, Coxiella burnetii resulted in
the increased expression of transferrin receptors TfR in the murine macrop
hage-like cell line J774A.1. This upregulation was evident in immunoblots a
s early as 6 h postinfection, with TfR levels continuing to increase throug
h the first 24 h of infection, Fluorescent labeling revealed that TfR upreg
ulation occurred throughout infected monolayers, eliminating the possibilit
y that it reflected a response by a minor subset of host cells. In addition
, TfR trafficking did not appear to be affected by C. burnetii infection. C
onsistent with the increase in TfRs, inoculation with viable C. burnetii re
sulted in a 2.5-fold increase in total cellular iron by 12 h postinoculatio
n. Our further findings that the chelation of intracellular iron arrests C.
burnetii replication and that C. burnetii metabolic activities in vitro ar
e affected by iron concentration suggest that TfR upregulation is a salient
factor in C. burnetii infection, and we speculate that it may represent a
significant virulence mechanism.