Myeloid PTEN promotes inflammation but impairs bactericidal activities during murine pneumococcal pneumonia
| Autor: | Ulrich Matt, Eva Hainzl, Immanuel Elbau, Bernd R. Binder, Joanna Warszawska, Bianca Doninger, Ildiko Mesteri, Gernot Schabbauer, Tanja Furtner, Sylvia Knapp, Philipp Günzl |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Blood Bactericidal Activity Myeloid Phagocytosis Immunology Colony Count Microbial Down-Regulation Inflammation Mice Transgenic Biology Mice Phosphatidylinositol 3-Kinases Immune system Cell Line Tumor Macrophages Alveolar medicine Immunology and Allergy Tensin PTEN Animals Myeloid Cells PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Mice Knockout Tumor Necrosis Factor-alpha PTEN Phosphohydrolase Pneumonia Pneumococcal medicine.disease Interleukin-10 Up-Regulation Mice Inbred C57BL medicine.anatomical_structure Streptococcus pneumoniae Pneumococcal pneumonia Cancer research biology.protein medicine.symptom Inflammation Mediators |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 185(1) |
| ISSN: | 1550-6606 |
| Popis: | Phosphatidylinositol 3-kinase has been described as an essential signaling component involved in the chemotactic cell influx that is required to eliminate pathogens. At the same time, PI3K was reported to modulate the immune response, thus limiting the magnitude of acute inflammation. The precise role of the PI3K pathway and its endogenous antagonist phosphatase and tensin homolog deleted on chromosome 10 (PTEN) during clinically relevant bacterial infections is still poorly understood. Utilizing mice lacking myeloid cell-specific PTEN, we studied the impact of PTEN on the immune response to Streptococcus pneumoniae. Survival analysis disclosed that PTEN-deficient mice displayed less severe signs of disease and prolonged survival. The inflammatory response to S. pneumoniae was greatly reduced in macrophages in vitro and in vivo. Unexpectedly, neutrophil influx to the lungs was significantly impaired in animals lacking myeloid-cell PTEN, whereas the additional observation of improved phagocytosis by alveolar macrophages lacking PTEN ultimately resulted in unaltered lung CFUs following bacterial infection. Together, the absence of myeloid cell-associated PTEN and consecutively enhanced PI3K activity dampened pulmonary inflammation, reduced neutrophil influx, and augmented phagocytic properties of macrophages, which ultimately resulted in decreased tissue injury and improved survival during murine pneumococcal pneumonia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|