CD36 provides host protection against klebsiella pneumoniae intrapulmonary infection by enhancing lipopolysaccharide responsiveness and macrophage phagocytosis

Tolani F. Olonisakin, Huihua Li, Zeyu Xiong, Elizabeth J.K. Kochman, Minting Yu, Yanyan Qu, Mei Hulver, Jay K. Kolls, Claudette St Croix, Yohei Doi, Minh Hong Nguyen, Robert M.Q. Shanks, Rama K. Mallampalli, Valerian E. Kagan, Anuradha Ray, Roy L. Silverstein, Prabir Ray, Janet S. Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 languageEnglish
Pages (from-to)1865-1875
Number of pages11
JournalJournal of Infectious Diseases
Volume214
Issue number12
DOIs
Publication statusPublished - 01-12-2016

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Klebsiella pneumoniae
Phagocytosis
Lipopolysaccharides
Macrophages
Infection
Virulence
Polysaccharides
Scavenger Receptors
Serum
Capsules
Cytokines
Ligands
Antigens
Mutation
Research

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Cite this

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. / CD36 provides host protection against klebsiella pneumoniae intrapulmonary infection by enhancing lipopolysaccharide responsiveness and macrophage phagocytosis. In: Journal of Infectious Diseases. 2016 ; Vol. 214, No. 12. pp. 1865-1875.
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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.",
author = "Olonisakin, {Tolani F.} and Huihua Li and Zeyu Xiong and Kochman, {Elizabeth J.K.} and Minting Yu and Yanyan Qu and Mei Hulver and Kolls, {Jay K.} and {St Croix}, Claudette and Yohei Doi and Nguyen, {Minh Hong} and Shanks, {Robert M.Q.} and Mallampalli, {Rama K.} and Kagan, {Valerian E.} and Anuradha Ray and Silverstein, {Roy L.} and Prabir Ray and Lee, {Janet S.}",
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Olonisakin, TF, Li, H, Xiong, Z, Kochman, EJK, Yu, M, Qu, Y, Hulver, M, Kolls, JK, St Croix, C, Doi, Y, Nguyen, MH, Shanks, RMQ, Mallampalli, RK, Kagan, VE, Ray, A, Silverstein, RL, Ray, P & Lee, JS 2016, 'CD36 provides host protection against klebsiella pneumoniae intrapulmonary infection by enhancing lipopolysaccharide responsiveness and macrophage phagocytosis', Journal of Infectious Diseases, vol. 214, no. 12, pp. 1865-1875. https://doi.org/10.1093/infdis/jiw451

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 journalArticle

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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

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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.

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