IFNγ induces monopoiesis and inhibits neutrophil development during inflammation

Abstract

Steady-state hematopoiesis is altered on infection, but the cellular and molecular mechanisms driving these changes are largely unknown. Modulation of hematopoiesis is essential to increase the output of the appropriate type of effector cell required to combat the invading pathogen. In the present study, we demonstrate that the pro-inflammatory cytokine IFN␥ is involved in orchestrating inflammationinduced myelopoiesis. Using both mouse models and in vitro assays, we show that IFN␥ induces the differentiation of monocytes over neutrophils at the level of myeloid progenitors. Infection with lymphocytic choriomeningitis virus induces monopoiesis in wild-type mice, but causes increased neutrophil production in IFN␥ ؊/؊ mice. We demonstrate that IFN␥ enhances the expression of the monopoiesis-inducing transcription factors IRF8 and PU.1 in myeloid progenitor cells, whereas it reduces G-CSF-driven neutrophil differentiation via a SOCS3-dependent inhibition of STAT3 phosphorylation. These results establish a critical role for IFN␥ in directing monocyte versus neutrophil development during immune activation. (Blood. 2012;119(6): 1543-1554)

Aging and the immune response to organ transplantation

“…A similar trend is observed with other organ transplants: approximately 50% of patients who received cardiac transplants between 2002 and 2010 were over 50 years of age, and over 20% were older than 60 years (2). Along these lines, clinical studies have demonstrated that solid-organ transplantation is an effective treatment for selected older patients (3)(4)(5)(6)(7)(8). However, older transplant recipients succumb to more infections and are more susceptible to post-transplant malignancies (9,10).…”

Microbiota-Derived Compounds Drive Steady-State Granulopoiesis via MyD88/TICAM Signaling

“…This process appears to require sensing of pathogen-associated molecular patterns in a TLR-dependent manner (7). It is further known that massive production of IFN-g can enhance the production of monocytes over granulocytes and can drive erythropoiesis to start at sites outside the bone marrow (BM) (8). However, increased production of mature granulocytes requires hours to days in the human system, and although this increased production is central to the later control and eradication of infection, the initial encounter with pathogenic or apathogenic bacteria requires the immediate action of the homeostatically maintained circulating and marginated granulocyte pools (1,6).…”

Cytokine Regulation of Respiratory Burst in Blood Neutrophils for Prediction of Abdominal Sepsis in Patients With Extended Purulent Peritonitis

“…Вместе с тем содержание IFNγ у боль-ных с послеоперационным абдоминальным сеп-сисом в 1,9 раза выше, чем у пациентов, у кото-рых послеоперационный период будет протекать без осложнений. Известно, что IFNγ ингибирует развитие нейтрофильных гранулоцитов в ди-намике воспалительной реакции [9]. Соответ-ственно, исходя из выявленных взаимосвязей между уровнями концентраций цитокинов и по-казателей респираторного взрыва нейтрофилов, можно заключить, что у здоровых людей при уве-личении концентрации IFNγ ингибирует спон-танный и индуцированный синтез вторичных АФК.…”