title: Chitinase 3-like-1 promotes Streptococcus pneumoniae killing and augments host tolerance to lung antibacterial responses.
abstract: Host antibacterial responses include mechanisms that kill bacteria, but also those that protect or tolerize the host to potentially damaging antibacterial effects. We determined that Chitinase 3-like-1 (Chi3l1), a conserved prototypic chitinase-like protein, is induced by Streptococcus pneumoniae and plays central roles in promoting bacterial clearance and mediating host tolerance. S. pneumoniae-infected Chi3l1 null mice exhibit exaggerated lung injury, inflammation and hemorrhage, more frequent bacterial dissemination, decreased bacterial clearance, and enhanced mortality compared to controls. Chi3l1 augments macrophage bacterial killing by inhibiting caspase-1-dependent macrophage pyroptosis and augments host tolerance by controlling inflammasome activation, ATP accumulation, expression of ATP receptor P2X7R, and production of thymic stromal lymphopoietin and type 1, type 2, and type 17 cytokines. These data demonstrate that Chi3l1 is induced during infection, where it promotes bacterial clearance while simultaneously augmenting host tolerance, and that these roles likely contributed to the retention of Chi3l1 over species and evolutionary time.
authors: Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. charles.delacruz@yale.edu
authors: Charles S
authors: CS
authors: Dela Cruz
authors: Wei
authors: W
authors: Liu
authors: Chuan Hua
authors: CH
authors: He
authors: Adam
authors: A
authors: Jacoby
authors: Alex
authors: A
authors: Gornitzky
authors: Bing
authors: B
authors: Ma
authors: Richard
authors: R
authors: Flavell
authors: Chun Geun
authors: CG
authors: Lee
authors: Jack A
authors: JA
authors: Elias
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D016923:Cell Death; D000071451:Chitinase-3-Like Protein 1; D016207:Cytokines / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D058847:Inflammasomes / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008817:Mice, Mutant Strains; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D011018:Pneumonia, Pneumococcal / Q000378:metabolism / Q000503:physiopathology; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*
chemical_list: D002352:Carrier Proteins; C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D016207:Cytokines; D006023:Glycoproteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D020170:Caspase 1