Journal Article

Deficiency in Galectin-3, -8, and -9 impairs immunity to chronic Mycobacterium tuberculosis infection but not acute infection with multiple intracellular pathogens

Penn, Bennett H., Van Dis, Erik, Bell, Samantha L., Stanley, Sarah A., Craft, Julia, Portnoy, Daniel A., Cox, Jeffery S., Dodd, Claire E., Morrison, Huntly M., Vance, Russell E., Beatty, Wandy L., Krogan, Nevan J., Shaker, Isaac, Watson, Robert O., Margolis, Shally R., Repasy, Teresa, Johnson, Jeffery R., Lee, Angus Y., Rivera-Lugo, Rafael, Golovkine, Guillaume R.

2023

Overview

Macrophages employ an array of pattern recognition receptors to detect and eliminate intracellular pathogens that access the cytosol. The cytosolic carbohydrate sensors Galectin-3, -8, and -9 (Gal-3, Gal-8, and Gal-9) recognize damaged pathogen-containing phagosomes, and Gal-3 and Gal-8 are reported to restrict bacterial growth via autophagy in cultured cells. However, the contribution of these galectins to host resistance during bacterial infection in vivo remains unclear. We found that Gal-9 binds directly to Mycobacterium tuberculosis ( Mtb ) and Salmonella enterica serovar Typhimurium ( Stm ) and localizes to Mtb in macrophages. To determine the combined contribution of membrane damage-sensing galectins to immunity, we generated Gal-3, -8, and -9 triple knockout (TKO) mice. Mtb infection of primary macrophages from TKO mice resulted in defective autophagic flux but normal bacterial replication. Surprisingly, these mice had no discernable defect in resistance to acute infection with Mtb , Stm or Listeria monocytogenes , and had only modest impairments in bacterial growth restriction and CD4 T cell activation during chronic Mtb infection. Collectively, these findings indicate that while Gal-3, -8, and -9 respond to an array of intracellular pathogens, together these membrane damage-sensing galectins play a limited role in host resistance to bacterial infection.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Arrays / Autophagy / Bacteria / Bacterial diseases / Bacterial infections / Biology and Life Sciences / Carbohydrates / Care and treatment / CD4 antigen / Cell activation / Cell death / Chronic infection / Control / Cytosol / Damage / Diagnosis / Disease susceptibility / Drug resistance in microorganisms / Engineering and Technology / Experiments / Galectin-3 / Health aspects / Identification and classification / Immune response / Immunity / Infections / Intracellular / Listeria / Listeria monocytogenes / Lymphocytes / Lymphocytes T / Macrophages / Mass spectrometry / Medical research / Medicine and Health Sciences / Medicine, Experimental / Membranes / Microscopy / Mycobacterium tuberculosis / Pathogenic microorganisms / Pathogens / Pattern recognition / Pattern recognition receptors / Phagocytosis / Phagosomes / Prevention / Proteins / Salmonella / Salmonella Typhimurium / Scientific imaging / T cells / Tuberculosis