Integrin receptors play a role in the internalin B-dependent entry of Listeria monocytogenes into host cells.
Listeria monocytogenes enters non-phagocytic cells by binding its surface proteins inlA (internalin) and inlB to the host's E-cadherin and Met, respectively. The two internalins play either separate or cooperative roles in the colonization of infected tissues. Here, we studied bacterial uptake into HeLa cells using an L. monocytogenes mutant strain (DeltainlA) carrying a deletion in the gene coding for inlA. The DeltainlA mutant strain showed the capability to invade HeLa cells. The monoclonal anti-beta(3)- and anti-beta(1)-integrin subunit antibodies prevented bacterial uptake into the cells, while the anti-beta(2)- and anti-beta(4)-integrin subunit antibodies failed to affect L. monocytogenes entry into HeLa cells. Three structurally distinct disintegrins (kistrin, echistatin and flavoridin) also inhibited bacterial uptake, showing different potencies correlated to their selective affinity for the beta(3)- and beta(1)-integrin subunits. In addition to inducing Met phosphorylation, infection of cells by the L. monocytogenes DeltainlA mutant strain promoted the tyrosine phosphorylation of the focal adhesion-associated proteins FAK and paxillin. Our findings provide the first evidence that beta(3)- and beta(1)-integrin receptors play a role in the inlB-dependent internalization of L. monocytogenes into host cells.
Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Italy.
Clementina
C
Auriemma
Maurizio
M
Viscardi
Simona
S
Tafuri
Luigi Michele
LM
Pavone
Federico
F
Capuano
Laura
L
Rinaldi
Rossella
R
Della Morte
Giuseppe
G
Iovane
Norma
N
Staiano
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019483:Disintegrins / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D039661:Integrin beta3 / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D019483:Disintegrins; D019012:Integrin beta1; D039661:Integrin beta3; D008565:Membrane Proteins; D051419:Paxillin; C095768:inlB protein, Listeria monocytogenes; C069761:internalin protein, Bacteria; D019859:Proto-Oncogene Proteins c-met; D051417:Focal Adhesion Kinase 1