Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection.
Infection with Listeria monocytogenes causes lymphocyte apoptosis that is mediated by the actions of the pore-forming virulence factor listeriolysin O (LLO). Previous work showed that activated lymphocytes were highly sensitive to LLO-induced apoptosis, whereas resting lymphocytes were less susceptible. We now show that mice deficient in the type I interferon (IFN) receptor were more resistant to Listeria infection and had less apoptotic lesions than wild-type counterparts. Furthermore, treatment of resting splenic lymphocytes with recombinant IFN-alphaA enhanced their susceptibility to LLO-induced apoptosis. Together, these data suggest that type I IFN signaling is detrimental to handling of a bacterial pathogen and may enhance the susceptibility of lymphocytes undergoing apoptosis in response to bacterial pore-forming toxins.
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110, USA.
Javier A
JA
Carrero
Boris
B
Calderon
Emil R
ER
Unanue
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004801:Eosine Yellowish-(YS); D006360:Heat-Shock Proteins / Q000276:immunology; D006416:Hematoxylin; D006460:Hemolysin Proteins; D020287:In Situ Nick-End Labeling; D007370:Interferon Type I / Q000276:immunology / Q000494:pharmacology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice / Q000276:immunology*; D008817:Mice, Mutant Strains; D017471:Receptors, Interferon / Q000172:deficiency*; D015398:Signal Transduction; D013154:Spleen / Q000473:pathology
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D007370:Interferon Type I; D017471:Receptors, Interferon; C038705:hlyA protein, Listeria monocytogenes; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin