Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases

Abstract

Galectin-9 (Gal-9) is a β-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.

A Case of COVID-19 with Acute Exacerbation after Anti-Inflammatory Treatment

“…Gal-9 is expressed in endothelial cells, the epithelium of the gastrointestinal tract, and several immune cells, including T cells, B cells, macrophages, mast cells, and dendritic cells. Gal-9 regulates the transduction of intra-and extracellular signals by interacting with several receptors [21]. While the inflammatory marker was not deregulated in this case, only Gal-9 was elevated followed by a decline associated with the deterioration and recovery of the respiratory conditions.…”

“…Only the Gal-9 level was elevated with the deterioration in the respiratory condition and returned to a normal level with its improvement. We already reported that the plasma level of Gal-9 is a representative inflammatory biomarker in COVID-19, tuberculosis, and HIV infections [21]. In addition, Gal-9 may reflect the severity of acute and chronic infectious diseases.…”

Seminar Lessons: Infectious Diseases Associated with and Causing Disaster

“…In addition, the significance of matricellular proteins such as OPN and Gal-9, which were reported as markers of severity for tropical infectious diseases, was reconfirmed in COVID-19 infection. Further examination revealed that protease cleaves these proteins, suggesting that cleaved products exert new pathological functions and become new severity mark-ers [54,55]. On the other hand, the countermeasures against COVID-19, which caused the disasters worldwide, have introduced a great deal of knowledge about the pathophysiology and infectious mode of disaster-related infectious diseases.…”

Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases

“…Furthermore, both diseases are accompanied by cytokine storms. Both proinflammatory and anti-inflammatory cytokines and chemokines are induced during the progression of DENV infection, suggesting that multifunctional mediators are involved in the associated pathogenesis [142,147,148].…”