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

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...

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Bibliographic Details
Published in:PLoS pathogens 2023-06, Vol.19 (6), p.e1011088-e1011088
Main Authors: Morrison, Huntly M, Craft, Julia, Rivera-Lugo, Rafael, Johnson, Jeffery R, Golovkine, Guillaume R, Bell, Samantha L, Dodd, Claire E, Van Dis, Erik, Beatty, Wandy L, Margolis, Shally R, Repasy, Teresa, Shaker, Isaac, Lee, Angus Y, Vance, Russell E, Stanley, Sarah A, Watson, Robert O, Krogan, Nevan J, Portnoy, Daniel A, Penn, Bennett H, Cox, Jeffery S
Format: Article
Language:English
Subjects:
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
Identification and classification
Immunity
Infections
Intracellular
Listeria
Listeria monocytogenes
Lymphocytes
Lymphocytes T
Macrophages
Mass spectrometry
Medicine and Health Sciences
Membranes
Microscopy
Mycobacterium tuberculosis
Pathogenic microorganisms
Pathogens
Pattern recognition
Pattern recognition receptors
Phagocytosis
Phagosomes
Prevention
Proteins
Salmonella
Salmonella Typhimurium
Scientific imaging
Tuberculosis
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1011088