Impaired bacterial clearance in type 3 deiodinase-deficient mice infected with Streptococcus pneumoniae.
The activation of type 3 deiodinase (D3) has been postulated to play a role in the reduction of thyroid hormone levels during illness. Using a mouse model of acute bacterial infection, we have recently demonstrated marked D3 immunostaining in neutrophils infiltrating infected organs. These observations suggest a possible additional role for this enzyme in the innate immune response. To further assess the role of D3 in the response to acute bacterial infection, we used null D3 [D3 knockout (D3KO)] and wild type (WT) mice and infected them with Streptococcus pneumoniae. Marked reductions in serum thyroid hormone levels were observed both in D3KO and WT mice. Infection resulted also in a decrease in liver D1 activity in WT, but not in infected D3KO mice. Upon infection, pulmonary neutrophilic influx (measured by myeloperoxidase levels) and IL-6 and TNF concentrations increased equally in D3KO and WT mice, and histological examination of infected mice showed similar pulmonary inflammation in both strains. However, D3KO animals demonstrated significantly higher bacterial load in blood, lung, and spleen compared with WT mice. We conclude that 1) D3 is not required to generate the systemic manifestations of the nonthyroidal illness syndrome in this model; 2) the lack of D3 does not affect the extent of pulmonary inflammation; and 3) bacterial outgrowth in blood, spleen, and lung of D3KO mice is significantly higher than in WT mice. Our results suggest a protective role for D3 in the defense against acute bacterial infection, probably by reinforcing the microbial killing capacity of neutrophils.
Boelen
Anita
A
Department of Endocrinology and Metabolism, F5-165, Academic Medical Center, Amsterdam, The Netherlands. a.boelen@amc.uva.nl
Kwakkel
Joan
J
Wieland
Catharina W
CW
St Germain
Donald L
DL
Fliers
Eric
E
Hernandez
Arturo
A
D000818:Animals; D005260:Female; D053583:Interleukin-1beta; D015850:Interleukin-6 / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics* / Q000502:physiology; D008099:Liver / Q000201:enzymology / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D011008:Pneumococcal Infections / Q000097:blood / Q000235:genetics* / Q000382:microbiology; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000472:pathogenicity* / Q000502:physiology; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine