Rapid recruitment of neutrophils containing prestored IL-12 during microbial infection.
Neutrophils are well known to rapidly migrate to foci of infection, where they exert microbicidal functions. We sought to determine whether neutrophils responding to in vivo infection with the protozoan pathogen Toxoplasma gondii were capable of IL-12 production as suggested by recent in vitro studies. Intraperitoneal infection induced a neutrophil influx by 4 h, accompanied by ex vivo IL-12 p40 and p70 release. Approximately 85% of the neutrophils displayed intracellular stores of IL-12, as determined by flow cytometry and confocal fluorescence microscopy. Neutrophils from IFN-gamma knockout mice also expressed IL-12, ruling out an IFN-gamma-priming requirement. Neither infected nor uninfected peritoneal macrophages displayed intracellular IL-12, but these cells were strongly IL-10(+). Infection per se was unnecessary for IL-12 production because peritoneal and peripheral blood neutrophils from uninfected animals contained IL-12(+) populations. Expression of the granulocyte maturation marker Gr-1 (Ly-6G) was correlated with IL-12 production. Mice depleted of their granulocytes by mAb administration at the time of infection had decreased serum levels of IL-12 p40. These results suggest a model in which neutrophils with prestored IL-12 are rapidly mobilized to an infection site where they are triggered by the parasite to release cytokine. Our findings place neutrophils prominently in the cascade of early events leading to IL-12-dependent immunity to T. gondii.
Bliss
S K
SK
Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
Butcher
B A
BA
Denkers
E Y
EY
D000208:Acute Disease; D000818:Animals; D021461:Animals, Outbred Strains; D000950:Antigens, Ly / Q000096:biosynthesis; D002465:Cell Movement / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009503:Neutropenia / Q000276:immunology / Q000469:parasitology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D010538:Peritonitis / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D014122:Toxoplasma / Q000254:growth & development / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000473:pathology
D000950:Antigens, Ly; D016753:Interleukin-10; D018664:Interleukin-12