Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice.
Mice that lack the p85alpha regulatory subunit of phosphatidylinositol-3 kinase (PI3K) are deficient in gastrointestinal and peritoneal mast cells but have dermal mast cells. Accordingly, these mice show impaired bacterial clearance in response to acute septic peritonitis and are highly susceptible to infection by the intestinal nematode Strongyloides venezuelensis. Systemic anaphylactic shock responses, however, are intact. We found that although reconstitution of PI3Kminus sign/minus sign mice with bone marrow--derived mast cells (BMMCs) restored anti-bacterial immunity, only T helper type 2 (TH2)-conditioned BMMCs, not "standard" BMMCs, were able to restore anti-nematode immunity. This finding highlights the importance of the TH2 response in the control of nematode infection. Thus, PI3K likely plays an essential role in host immune responses by regulating both the development and induction of mast cells.
Fukao
Taro
T
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Yamada
Taketo
T
Tanabe
Masanobu
M
Terauchi
Yasuo
Y
Ota
Takayuki
T
Takayama
Tetsuro
T
Asano
Tomoichiro
T
Takeuchi
Tsutomu
T
Kadowaki
Takashi
T
Hata Ji
Jun-ichi
J
Koyasu
Shigeo
S
D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004064:Digestive System / Q000276:immunology* / Q000473:pathology; D007113:Immunity, Innate; D008214:Lymphocytes / Q000276:immunology; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013322:Strongyloidiasis / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D019869:Phosphatidylinositol 3-Kinases; D019009:Proto-Oncogene Proteins c-kit