Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1865-1875 |
| Number of pages | 11 |
| Journal | Journal of Infectious Diseases |
| Volume | 214 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 01-12-2016 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Infectious Diseases
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CD36 provides host protection against klebsiella pneumoniae intrapulmonary infection by enhancing lipopolysaccharide responsiveness and macrophage phagocytosis. / Olonisakin, Tolani F.; Li, Huihua; Xiong, Zeyu; Kochman, Elizabeth J.K.; Yu, Minting; Qu, Yanyan; Hulver, Mei; Kolls, Jay K.; St Croix, Claudette; Doi, Yohei; Nguyen, Minh Hong; Shanks, Robert M.Q.; Mallampalli, Rama K.; Kagan, Valerian E.; Ray, Anuradha; Silverstein, Roy L.; Ray, Prabir; Lee, Janet S.
In: Journal of Infectious Diseases, Vol. 214, No. 12, 01.12.2016, p. 1865-1875.Research output: Contribution to journal › Article
TY - JOUR
T1 - CD36 provides host protection against klebsiella pneumoniae intrapulmonary infection by enhancing lipopolysaccharide responsiveness and macrophage phagocytosis
AU - Olonisakin, Tolani F.
AU - Li, Huihua
AU - Xiong, Zeyu
AU - Kochman, Elizabeth J.K.
AU - Yu, Minting
AU - Qu, Yanyan
AU - Hulver, Mei
AU - Kolls, Jay K.
AU - St Croix, Claudette
AU - Doi, Yohei
AU - Nguyen, Minh Hong
AU - Shanks, Robert M.Q.
AU - Mallampalli, Rama K.
AU - Kagan, Valerian E.
AU - Ray, Anuradha
AU - Silverstein, Roy L.
AU - Ray, Prabir
AU - Lee, Janet S.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85016050287&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85016050287&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiw451
DO - 10.1093/infdis/jiw451
M3 - Article
C2 - 27683817
AN - SCOPUS:85016050287
VL - 214
SP - 1865
EP - 1875
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 12
ER -