Role of Janus kinase 3 in mast cell-mediated innate immunity against gram-negative bacteria.
Mast cells play a pivotal role in innate host immune response to gram-negative bacteria. We report that Janus kinase 3 plays a role in mast cell-mediated bacterial clearance and neutrophil recruitment by regulating the release of tumor necrosis factor from mast cells. The role of JAK3 in mast cell-facilitated neutrophil recruitment and bacterial clearance was investigated by comparing the neutrophil influxes and bacterial clearance in mast cell-deficient W/W(v) mice reconstituted with JAK3(+/+) or JAK(-/-) mast cells. The neutrophil influx, bacterial clearance, and survival outcome in W/W(v) mice reconstituted with JAK3(+/+) mast cells was better than in W/W(v) mice reconstituted with JAK3(-/-) mast cells. These findings provide evidence that JAK3 is a key regulator of mast cell-mediated innate immunity against gram-negative bacteria.
Malaviya
R
R
Department of Allergy and Inflammatory Diseases, 2665 Long Lake Road, St. Paul, MN 55113, USA. malaviya2@ih.org
Navara
C
C
Uckun
F M
FM
D000818:Animals; D015703:Antigens, CD; D000071178:CD48 Antigen; D002634:Chemotaxis, Leukocyte; D004927:Escherichia coli Infections / Q000276:immunology* / Q000401:mortality; D016905:Gram-Negative Bacterial Infections / Q000276:immunology; D007113:Immunity, Innate; D053616:Janus Kinase 3; D008407:Mast Cells / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D010538:Peritonitis / Q000276:immunology* / Q000401:mortality; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D000071178:CD48 Antigen; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3