Tipping the balance: thyroid hormones as modulators of the sensitive harmony of innate immunity

Abstract Thyroid hormones (THs) are increasingly recognized as important regulators of innate immune cell function. As innate immune cells are essential for combating infections, TH status may, therefore, be a determinant of susceptibility to developing infections. Investigations into the effects of THs on various innate immune cells, including monocytes, macrophages, dendritic cells, and neutrophils, have revealed that these cells express all TH components and that their immune functions are modulated by TH status. Experimental studies in animals have demonstrated that hypothyroidism is associated with increased mortality during infections, largely due to impaired pathogen clearance and elevated pathogen loads. While the impact of THs on infection outcomes is well investigated in animal models, their role in human susceptibility to infection remains underappreciated. This review examines the clinical evidence for altered infection risk in both hypo- and hyperthyroid states, including rare syndromes of reduced sensitivity to thyroid hormone, and combines clinical data with mechanistic studies at the cellular level. Collectively, these findings highlight the critical role of THs in host defense and underscore the need for further research into their clinical relevance in human infectious diseases.