CD36 Provides Host Protection Against Klebsiella pneumoniae Intrapulmonary Infection by Enhancing Lipopolysaccharide Responsiveness and Macrophage Phagocytosis.
Klebsiella pneumoniae remains an important cause of intrapulmonary infection and invasive disease worldwide. K. pneumoniae can evade serum killing and phagocytosis primarily through the expression of a polysaccharide capsule, but its pathogenicity is also influenced by host factors. We examined whether CD36, a scavenger receptor that recognizes pathogen and modified self ligands, is a host determinant of K. pneumoniae pathogenicity. Despite differences in serum sensitivity and virulence of 3 distinct K. pneumoniae (hypermucoviscous K1, research K2, and carbapenemase-producing ST258) strains, the absence of CD36 significantly increased host susceptibility to acute intrapulmonary infection by K. pneumoniae, regardless of strain. We demonstrate that CD36 enhances LPS responsiveness to K. pneumoniae to increase downstream cytokine production and macrophage phagocytosis that is independent of polysaccharide capsular antigen. Our study provides new insights into host determinants of K. pneumoniae pathogenicity and raises the possibility that functional mutations in CD36 may predispose individuals to K. pneumoniae syndromes.
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Tolani F
TF
Olonisakin
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Huihua
H
Li
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Zeyu
Z
Xiong
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Elizabeth J K
EJ
Kochman
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Minting
M
Yu
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Yanyan
Y
Qu
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Mei
M
Hulver
Children's Hospital of Pittsburgh.
Jay K
JK
Kolls
Center for Biologic Imaging.
Claudette
C
St Croix
Division of Infectious Diseases.
Yohei
Y
Doi
Division of Infectious Diseases.
Minh-Hong
MH
Nguyen
Department of Ophthalmology.|Department of Microbiology and Molecular Genetics.
Robert M Q
RM
Shanks
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Rama K
RK
Mallampalli
Department of Environmental Occupational Health, Graduate School of Public Health.
Valerian E
VE
Kagan
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Anuradha
A
Ray
Department of Medicine, Medical College of Wisconsin.|Blood Research Institute, Blood Center of Wisconsin, Milwaukee.
Roy L
RL
Silverstein
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Prabir
P
Ray
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.|Vascular Medicine Institute, University of Pittsburgh, Pennsylvania.
Janet S
JS
Lee
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D005260:Female; D054884:Host-Pathogen Interactions; D007710:Klebsiella Infections / Q000276:immunology*; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000276:immunology
D018955:CD36 Antigens; D008070:Lipopolysaccharides
CD36; Klebsiella pneumoniae; host defense; hypermucoviscous strains; macrophage; multi-drug resistant K. pneumoniae; pneumonia
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