Toll-like receptor-MyD88 and Fc receptor pathways of mast cells mediate the thyroid dysfunctions observed during nonthyroidal illness.
Bacterial infections and other pathologic conditions induce complex dysfunctions of the hypothalamic-pituitary-thyroid axis, collectively known as nonthyroidal illness (NTI). To explore the pathogenesis of bacterial NTI, we injected Mycobacterium tuberculosis extracts or Escherichia coli LPS in mice lacking key components of the Toll-like receptor or crystallizable fragment (Fc) receptor pathways. In wild-type mice, the bacterial components induced a hypothyroidism characterized by elements of both hypothalamic and thyroidal dysfunction. This NTI hypothyroidism did not develop in mice lacking the MyD88 adaptor or in those with a reduced number of mast cells. The hypothyroid responsiveness to LPS, however, was restored upon reconstitution with mast cells derived from the bone marrow of wild-type donors. In addition to bacterial components, whole immunoglobulins induced NTI hypothyroidism in wild-type mice, but not in those lacking activating Fc receptors or mast cells. The study demonstrates a link between Toll-like and Fc receptor signaling and thyroid gland function, uncovering a role of mast cells in murine NTI.
Rocchi
Roberto
R
Department of Pathology and Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kimura
Hiroaki
H
Tzou
Shey-Cherng
SC
Suzuki
Koichi
K
Rose
Noel R
NR
Pinchera
Aldo
A
Ladenson
Paul W
PW
Caturegli
Patrizio
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000382:microbiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D015331:Cohort Studies; D005269:Femur / Q000166:cytology; D005620:Freund's Adjuvant / Q000494:pharmacology; D007037:Hypothyroidism / Q000209:etiology / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D013959:Thyroid Diseases / Q000378:metabolism* / Q000503:physiopathology; D013977:Tibia / Q000166:cytology
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D011961:Receptors, Fc; D005620:Freund's Adjuvant