The Interaction of Klebsiella pneumoniae With Lipid Rafts-Associated Cholesterol Increases Macrophage-Mediated Phagocytosis Due to Down Regulation of the Capsule Polysaccharide
Por:
Ares, Miguel A., Sansabas, Alejandro, Rodriguez-Valverde, Diana, Siqueiros-Cendon, Tania, Rascon-Cruz, Quintin, Rosales-Reyes, Roberto, Dolores Jarillo-Quijada, Ma., Alcantar-Curiel, Maria D., Cedillo, Maria L., Torres, Javier, Giron, Jorge A., De la Cruz, Miguel A.
Publicada:
17 jul 2019
Resumen:
Klebsiella pneumoniae successfully colonizes host tissues by recognizing
and interacting with cholesterol present on membrane-associated lipid
rafts. In this study, we evaluated the role of cholesterol in the
expression of capsule polysaccharide genes of K. pneumoniae and its
implication in resistance to phagocytosis. Our data revealed that
exogenous cholesterol added to K. pneumoniae increases
macrophage-mediated phagocytosis. To explain this event, the expression
of capsular galF, wzi, and manC genes was determined in the presence of
cholesterol. Down-regulation of these capsular genes occurred leading to
increased susceptibility to phagocytosis by macrophages. In contrast,
depletion of cholesterol from macrophage membranes led to enhanced
expression of galF, wzi, and manC genes and to capsule production
resulting in resistance to macrophage-mediated phagocytosis.
Cholesterol-mediated repression of capsular genes was dependent on the
RcsA and H-NS global regulators. Finally, cholesterol also
down-regulated the expression of genes responsible for LPS core
oligosaccharides production and OMPs. Our results suggest that
cholesterol plays an important role for the host by reducing the
anti-phagocytic properties of the K. pneumoniae capsule facilitating
bacterial engulfment by macrophages during the bacteria-eukaryotic cell
interaction mediated by lipid rafts.
Filiaciones:
Ares, Miguel A.:
Inst Mexicano Seguro Social, Unidad Invest Medica Enfermedades Infecciosas & P, Ctr Med Nacl Siglo XXI, Hosp Pediat, Mexico City, DF, Mexico
Sansabas, Alejandro:
Inst Mexicano Seguro Social, Unidad Invest Medica Enfermedades Infecciosas & P, Ctr Med Nacl Siglo XXI, Hosp Pediat, Mexico City, DF, Mexico
Univ Autonoma Chihuahua, Fac Ciencias Quim, Chihuahua, Mexico
Rodriguez-Valverde, Diana:
Inst Mexicano Seguro Social, Unidad Invest Medica Enfermedades Infecciosas & P, Ctr Med Nacl Siglo XXI, Hosp Pediat, Mexico City, DF, Mexico
Univ Autonoma Chihuahua, Fac Ciencias Quim, Chihuahua, Mexico
Siqueiros-Cendon, Tania:
Univ Autonoma Chihuahua, Fac Ciencias Quim, Chihuahua, Mexico
Rascon-Cruz, Quintin:
Univ Autonoma Chihuahua, Fac Ciencias Quim, Chihuahua, Mexico
Rosales-Reyes, Roberto:
Univ Nacl Autonoma Mexico, Fac Med, Unidad Med Expt, Mexico City, DF, Mexico
Dolores Jarillo-Quijada, Ma.:
Univ Nacl Autonoma Mexico, Fac Med, Unidad Med Expt, Mexico City, DF, Mexico
Alcantar-Curiel, Maria D.:
Univ Nacl Autonoma Mexico, Fac Med, Unidad Med Expt, Mexico City, DF, Mexico
Cedillo, Maria L.:
Benemerita Univ Autonoma Puebla, Ctr Detecc Biomol, Puebla, Mexico
Torres, Javier:
Inst Mexicano Seguro Social, Unidad Invest Medica Enfermedades Infecciosas & P, Ctr Med Nacl Siglo XXI, Hosp Pediat, Mexico City, DF, Mexico
Giron, Jorge A.:
Benemerita Univ Autonoma Puebla, Ctr Detecc Biomol, Puebla, Mexico
De la Cruz, Miguel A.:
Inst Mexicano Seguro Social, Unidad Invest Medica Enfermedades Infecciosas & P, Ctr Med Nacl Siglo XXI, Hosp Pediat, Mexico City, DF, Mexico
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